Phosphinite-oxazolines and metal complexes

ABSTRACT

Compounds of formulae I and Ia,  
                 
 
     wherein  
     X 1  is secondary phosphino; R 3  is hydrogen, a hydrocarbon radical having from 1 to 20 carbon atoms, a heterohydrocarbon radical, bonded via a carbon atom, having from 2 to 20 atoms and at least one hetero atom selected from the group O, S and NR, or ferrocenyl; R is H or C 1 -C 4 alkyl; each R 4  individually or both R 4  together are a hydrocarbon radical having from 1 to 20 carbon atoms; and R 01  and R 02  are each independently of the other a hydrogen atom or a hydrocarbon radical having from 1 to 20 carbon atoms, are chiral ligands for metal complexes with metals of sub-groups I and VIII, which are catalysts for asymmetric addition reactions, for example of hydrogen, to prochiral unsaturated organic compounds.

[0001] The present invention relates to chiralphosphinitemothyl-oxazolines; to a process for the preparation thereof;to intermediates used in the preparation thereof; to metal complexeswith metals selected from sub-groups I and VIII of the Periodic Table ofthe Elements (d-10 and d-8 metals, referred to as TM8 metalshereinbelow) and phosphinitomethyl-oxazolines as ligands; to a processfor asymmetric synthesis by means of an addition reaction betweenhydrogen, borohydrides or silanes and a carbon-carbon or carbon-heteroatom multiple bond in prochiral organic compounds or by means of anaddition reaction between C-nucleophiles or amines and allyliccompounds, especially for asymmetric hydrogenation of carbon-carbon orcarbon-hetero atom multiple bonds with hydrogen, in the presence ofcatalytic amounts of the metal complexes; and to the use of the metalcomplexes as catalysts for asymmetric synthesis by means of an additionreaction between hydrogen, borohydrides or silanes and a carbon-carbonor carbon-hetero atom multiple bond in prochiral organic compounds or bymeans of an addition reaction between C-nucleophiles or amines andallylic compounds, especially for asymmetric hydrogenation ofcarbon-carbon or carbon-hetero atom multiple bonds with hydrogen.

[0002] G. Helmchen and A. Pfaltz in Accounts of Chemical Research,Volume 33, Number 6, pages 336 to 345 (2000) describe chiralphosphinophenyl-oxazolines as P,N ligands for asymmetric catalysts thatare used inter alia in the enantioselective addition of nucleophiles tocarbon-carbon double bonds. The oxazoline ring is substituted with bulkygroups in the α-position to the nitrogen atom to form an asymmetriccentre (carbon atom).

[0003] It has been found, surprisingly, that it is possible to preparein simple manner P,N ligands that contain a phosphinitemethyl group inthe α-position to the nitrogen atom to form an asymmetric centre (carbonatom), which phosphinitemethyl group serves at the same time as achelating group. Those substituted oxazolines form with TM8 metalschiral complexes that are excellent catalysts for the enantioselectiveaddition of hydrogen, borohydrides or silanes to a carbon-carbon orcarbon-hetero atom multiple bond in prochiral organic compounds or ofC-nucleophiles or amines to allylic compounds or for theenantioselective coupling of aryl or alkenyl triflates to olefins (Heckreaction). Especially in the enantioselective hydrogenation of prochiralolefins catalysed with Ir complexes, particularly high optical yieldsare observed. In addition, the phosphinite groups in the ligands exhibita surprisingly high stability towards hydrolysis. The starting materialsfor the preparation of the ligands are simple, in some casescommercially available organic molecules that can be combined with oneanother in a variety of ways, so that the steric and electronicproperties of the ligands in respect of catalytic activity and stericselectivity can be adapted to the substrates to be reacted in anoutstanding manner.

[0004] The invention relates to compounds of formulae I and Ia,

[0005] wherein

[0006] X₁ is secondary phosphino;

[0007] R₃ is hydrogen, a hydrocarbon radical having from 1 to 20 carbonatoms, a heterohydrocarbon radical, bonded via a carbon atom, havingfrom 2 to 20 atoms and at least one hetero atom selected from the groupO, S and NR, or ferrocenyl;

[0008] R is H or C₁-C₄alkyl;

[0009] each R₄ individually or both R₄ together are a hydrocarbonradical having from 1 to 20 carbon atoms; and

[0010] R₀₁ and R₀₂ are each independently of the other a hydrogen atomor a hydrocarbon radical having from 1 to 20 carbon atoms.

[0011] The phosphine group X₁ may contain two identical or two differenthydrocarbon radicals or the two hydrocarbon radicals may form with the Patom a 3- to 8-membered ring. Preferably the phosphine group containstwo identical hydrocarbon radicals. The hydrocarbon radicals may beunsubstituted or substituted and they may contain from 1 to 22,preferably from 1 to 12, carbon atoms. Of the compounds of formulae Iand Ia special preference is given to those wherein the phosphine groupcontains two identical or different radicals selected from the group:linear or branched C₁-C₁₂alkyl; C₅-C₁₂cycloalkyl orC₅-C₁₂cycloalkyl-CH₂— unsubstituted or substituted by C₁-C₆alkyl or byC₁-C₆alkoxy; phenyl or benzyl; and phenyl or benzyl substituted byhalogen (for example F, Cl and Br), C₁-C₆alkyl, C₁-C₆haloalkyl (forexample trifluoromethyl), C₁-C6alkoxy, C₁-C₆haloalkoxy (for exampletrifluoromethoxy), (C₆H₅)₃Si, (C₁-C₁₂alkyl)₃Si, secondary amino or by—CO₂—C₁-C₆alkyl (for example —CO₂CH₃).

[0012] The two radicals in the phosphine group may together also bedimethylene, trimethylene, tetramethylene or pentamethyleneunsubstituted or substituted by halogen, C₁-C₆alkyl or by C₁-C₆alkoxy.The substituents are preferably bonded in the two ortho positions to theP atom.

[0013] The phosphine groups may also be those of formulae

[0014] wherein o and p are each independently of the other an integerfrom 2 to 10, and the sum of o+p is from 4 to 12, preferably from 5 to8, and the phenyl rings are unsubstituted or substituted by C₁-C₄alkyland C₁-C₄alkoxy. Examples are [3.3.1]- and [4.2.1]-phobyl of theformulae

[0015] Examples of secondary phosphine groups in which the twohydrocarbon radicals form with the P atom a 3- to 8-membered ring areespecially those of the formula

[0016] which may be substituted in one or both ortho positions andoptionally the meta positions to the P atom by C₁-C₄alkyl and/or byC₁-C₄alkoxy.

[0017] Examples of P substituents as alkyl, which preferably containsfrom 1 to 6 carbon atoms, are methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, tert-butyl, and the isomers of pentyl and hexyl.Examples of P substituents as unsubstituted or alkyl-substitutedcycloalkyl are cyclopentyl, cyclohexyl, methyl- and ethyl-cyclohexyl anddimethylcyclohexyl. Examples of P substituents as phenyl and benzylsubstituted by alkyl, alkoxy, haloalkyl and/or by haloalkoxy aremethylphenyl, dimethylphenyl, trimethylphenyl, ethylphenyl,methylbenzyl, methoxyphenyl, dimethoxyphenyl, trifluoromethylphenyl,bis-trifluoromethylphenyl, tris-trifluoromethylphenyl,trifluoromethoxyphenyl and bis-trifluoromethoxyphenyl.

[0018] Preferred phosphine groups X₁ are those which contain identicalor different, preferably identical, radicals selected from the groupC₁-C₆alkyl; cyclopentyl or cyclohexyl unsubstituted or substituted byfrom 1 to 3 C₁-C₄alkyl or C₁-C₄alkoxy substituents; benzyl andespecially phenyl, which are unsubstituted or substituted by from 1 to 3C₁-C₄alkyl, C₁-C₄alkoxy, F, Cl, C₁-C₄fluoroalkyl or C₁-C₄fluoroalkoxysubstituents.

[0019] In the compounds of formula I, X₁ is preferably the group —PR₁R₂wherein R₁ and R₂ are each independently of the other a hydrocarbonradical having from 1 to 20 carbon atoms, which is unsubstituted orsubstituted by halogen, C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkoxy,C₁-C₆haloalkoxy, (C₆H₅)₃Si, (C₁-C₁₂alkyl)₃Si or by —CO₂—C₁-C₆alkyl; orwherein R₁ and R₂ together are dimethylene, trimethylene, tetramethyleneor pentamethylene unsubstituted or substituted by C₁-C₄alkyl and/or byC₁-C₄alkoxy.

[0020] R₁ and R₂ are preferably identical or different, especiallyidentical, radicals selected from the group: branched C₃-C₆alkyl;cyclopentyl or cyclohexyl unsubstituted or substituted by from one tothree C₁-C₄alkyl or C₁-C₄alkoxy substituents; benzyl unsubstituted orsubstituted by from one to three C₁-C₄alkyl or C₁-C₄alkoxy substituents,and especially phenyl unsubstituted or substituted by from one to threeC₁-C₄alkyl, C₁-C₄alkoxy, —NH₂, OH, F, Cl, C₁-C₄fluoroalkyl orC₁-C₄fluoroalkoxy substituents.

[0021] R₁ and R₂ are more especially identical or different, especiallyidentical, radicals selected from the group: phenyl unsubstituted orsubstituted by from one to three C₁-C₄alkyl, C₁-C₄alkoxy orC₁-C₄fluoroalkyl substituents.

[0022] The radicals R₃ and R₄ may be unsubstituted or substituted, forexample by C₁-C₆alkyl, C₁-C₆alkoxy, cyclohexyl, C₆-C₁₀aryl,C₇-C₁₂aralkyl, C₁-C₄alkyl-C₆-C₁₀aryl, C₁-C₄alkoxy-C₆-C₁₀aryl,C₁-C₄alkyl-C₇-C₁₂aralkyl, C₁-C₄alkoxy-C₇-C₁₂aralkyl, —CO—OR₅, —CO—NR₆R₇or by —NR₆R₇, wherein R₅ is H, an alkali metal, C₁-C₆alkyl, cyclohexyl,phenyl or benzyl, and R₆ and R₇ are each independently of the otherhydrogen, C₁-C₆alkyl, cyclohexyl, phenyl or benzyl, or R₆ and R₇together are tetramethylene, pentamethylene or 3-oxapentylene.

[0023] The hydrocarbon radical R₃ contains preferably from 1 to 16, moreespecially from 1 to 12, carbon atoms. The hydrocarbon radical R₃ may beC₁-C₁₈alkyl, preferably C₁-C₁₂alkyl and more especially C₁-C₈alkyl;C₃-C₁₂cycloalkyl, preferably C₄-C₈cycloalkyl and more especiallyC₅-C₆cycloalkyl; or C₆-C₁₆aryl and preferably C₆-C₁₂aryl.

[0024] When R₃ is alkyl, it is preferably branched C₃-C₈alkyl. Examplesof alkyl are methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl,nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl,hexadecyl, heptadecyl, octadecyl and eicosyl. Preferred alkyl isisopropyl, isobutyl, tert-butyl, isopentyl, isohexyl and1,1,2,2-tetramethylethyl.

[0025] When R₃ is cycloalkyl, it may be, for example, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecylor cyclododecyl.

[0026] When R₃ is aryl, it may be, for example, phenyl, naphthyl,anthracenyl, phenanthryl, biphenyl or ferrocenyl.

[0027] The heterohydrocarbon radical R₃ contains preferably a total offrom 1 to 16, more especially a total of from 1 to 12, atoms and from 1to 3 hetero atoms selected from the group O, S and NR. Theheterohydrocarbon radical R₃ may be C₁-C₁₈heteroalkyl, preferablyC₁-C₁₂heteroalkyl and more especially C₁-C₈heteroalkyl;C₃-C₁₂heterocycloalkyl, preferably C₄-C₈heterocycloalkyl and moreespecially C₄-C₅heterocycloalkyl; or C₄-C₁₆heteroaryl and preferablyC₄-C₁₁heteroaryl.

[0028] When R₃ is ferrocenyl, the ferrocenyl is unsubstituted orsubstituted by at least one C₁-C₄alkyl, C₁-C₄alkoxy, trimethylsilyl orhalogen substituent, for example methyl, ethyl, n- or iso-propyl, butyl,methoxy, ethoxy, F, Cl or Br.

[0029] When R₃ is alkyl, it is preferably C₁-C₈alkyl. Examples ofheteroalkyl are methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl,ethoxypropyl, isopropoxymethyl, isopropoxyethyl, isobutoxyethyl,tert-butoxyethyl, methylthioethyl and dimethylaminoethyl.

[0030] When R₃ is heterocycloalkyl, it may be, for example, oxetanyl,tetrahydrofuranyl, oxacyclohexyl, dioxanyl, pyrrolidinyl orN-methylazacyclohexyl.

[0031] When R₃ is heteroaryl, it may be, for example, furanyl,thiophenyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl orquinoxalinyl.

[0032] In a preferred sub-group, R₃ is a hydrocarbon radical selectedfrom the group: branched C₃-C₁₂alkyl, C₅-C₆cycloalkyl, ferrocenyl andC₆-C₁₂aryl, the cyclic radicals being unsubstituted or substituted byhalogen (F, Cl, Br), C₁-C₄alkyl or by C₁-C₄alkoxy.

[0033] R₄ as a hydrocarbon radical contains preferably from 1 to 16,especially from 1 to 12, more especially from 1 to 8, carbon atoms. Thehydrocarbon radical R₄ may be C₁-C₁₈alkyl, preferably C₁-C₁₂alkyl andmore especially C₁-C₈alkyl; C₃-C₁₂cycloalkyl, preferablyC₄-C₈-cycloalkyl and more especially C₅-C₆cycloalkyl; C₆-C₁₆aryl andpreferably C₆-C₁₂aryl, or C₇-C₁₆aralkyl and preferably C₇-C₁₂aralkyl.

[0034] When the two R₄ are a hydrocarbon radical, that radical isalkylene, which preferably contains from 3 to 7, more especially from 4to 6, carbon atoms. Examples are 1,3-propylene, 1,3- or 1,4-butylene,1,3-, 1,4- or 1,5-pentylene and 1,3-, 1,4-, 1,5-, 2,5-, 2,6- or1,6-hexylene.

[0035] The embodiments and preferences given for R₃ apply to R₄ inrespect of alkyl, cycloalkyl and aryl. When R₄ is aralkyl, it ispreferably benzyl or naphthylmethyl, which are unsubstituted orsubstituted by halogen (F, Cl, Br), C₁-C₄alkyl or by C₁-C₄alkoxy.

[0036] In a preferred sub-group, R₄ is a hydrocarbon radical selectedfrom the group: branched C₃-C₁₂alkyl, C₅-C₆cycloalkyl, C₆-Cl₂aryl andC₇-C₁₂aralkyl, the cyclic radicals being unsubstituted or substituted byhalogen (F, Cl, Br), C₁-C₄alkyl, C₁-C₄haloalkyl (for exampletrifluoromethyl) or by C₁-C₄alkoxy.

[0037] The embodiments and preferences given for R₄ apply independentlyto R₀₁ and R₀₂. When R₀₁ and R₀₂ are different radicals or one of R₀₁and R₀₂ is a hydrogen atom, the compounds of formulae I and la contain afurther chiral carbon atom. The invention relates also to racemates ordiastereoisomers of those compounds. The relative configuration of thediastereoisomers may have a positive influence on the enantioselectivityin addition reactions catalysed according to the invention. R₀₁ and R₀₂are preferably each hydrogen. In another preferred group, R₀₁ ishydrogen and R₀₂ is C₁-C₄alkyl.

[0038] A preferred sub-group of the compounds according to the inventioncomprises those of formulae Ib and Ic,

[0039] wherein

[0040] X₁ is —PR₁R₂,

[0041] R₁ and R₂ are identical or different, especially identical,radicals selected from the group: α-branched C₃-C₆alkyl; C₅-C₇cycloalkylunsubstituted or substituted by from one to three C₁-C₄alkyl orC₁-C₄alkoxy substituents; phenyl unsubstituted or substituted by fromone to three C₁-C₄alkyl, C₁-C₄alkoxy or C₁-C₄fluoroalkyl substituents;and dimethylene, trimethylene, tetramethylene or hexamethyleneunsubstituted or substituted by C₁-C₄alkyl or by C₁-C₄alkoxy;

[0042] R₃ is a hydrocarbon radical selected from the group: branchedC₃-C₁₂alkyl, C₅-C₆cycloalkyl, C₆-C₁₂aryl and ferrocenyl, the cyclicradicals being unsubstituted or substituted by halogen, C₁-C₄alkyl,C₁-C₄haloalkyl or by C₁-C₄alkoxy; and

[0043] R₄ is a hydrocarbon radical selected from the group: branchedC₃-C₁₂alkyl, C₅-C₆cycloalkyl, C₆-C₁₂aryl and C₇-C₁₂aralkyl, the cyclicradicals being unsubstituted or substituted by halogen, C₁-C₄alkyl or byC₁-C₄alkoxy.

[0044] The compounds of formulae I and Ia can be prepared in a smallnumber of process steps in two different ways,α-amino-β-hydroxycarboxylic acid esters being a fundamental reagent. Ina first variant, iminocarboxylic acid esters are cyclised withα-amino-β-hydroxycarboxylic acid esters to form oxazolinecarboxylic acidesters, the ester group is then converted into a tertiary alcohol group,and subsequently the phosphonite is formed. In a second variant, acarboxylic acid or a carboxylic acid derivative is reacted with anα-amino-β-hydroxycarboxylic acid ester, the ester group is thenconverted into a tertiary alcohol group, cyclisation to the oxazoline iscarried out and subsequently the phosphonite is formed.

[0045] The invention relates also to a process for the preparation ofcompounds of formulae I and Ia,

[0046] wherein R₀₁, R₀₂, R₃, R₄ and X₁ are as defined above, and ˜denotes the R- or S-form, in which process either

[0047] a1) a compound of formula II

[0048]  or a salt thereof, wherein R₃ is as defined above and R₈ isC₁-C₄alkyl, is reacted with at least an equivalent amount of a compoundof formula III,

[0049] wherein R₉ is C₁-C₄alkyl, to form a compound of formula IV,

[0050] a2) the compound of formula IV is reacted with at least 2equivalents of an organometal compound of formula V or Va

R₄—X₂ (V), R₄—(X₂)₂ (Va),

[0051] wherein R₄ is as defined above, X₂ is an alkali metal or —Me₁X₃,Me₁ is Mg or Zn, and X₃ is Cl, Br or I, to form a compound of formula VI

[0052] and

[0053] a3) the hydroxyl group in the compound of formula VI ismetallated and then reacted with a halophosphine of formula VII,

X₁—Y₁  (VII),

[0054] wherein X₁ is as defined above and Y₁ is Cl, Br or I, to form acompound of formula Ia or Ib; or

[0055] b1) a carboxylic acid of formula VIII

R₃—COOH  (VIII),

[0056] or a derivative of that carboxylic acid, is reacted with acompound of formula III to form a carboxylic acid amide of formula IX,

[0057] b2) the compound of formula IX is reacted with a compound offormula V or Va to form a compound of formula X,

[0058] b3) the compound of formula X is cyclised to form a compound offormula VI; and

[0059] b4) the hydroxyl group in the compound of formula VI ismetallated and then reacted with a halophosphine of formula VII to forma compound of formula Ia or Ib.

[0060] The invention relates also to compounds of formula IV wherein R₀₁is a hydrogen atom and R₀₂ is a hydrocarbon radical having from 1 to 20carbon atoms, and R₃, R₄ and R₉ are as defined above.

[0061] The invention relates also to compounds of formula VI wherein R₀₁and R₀₂ are each independently of the other a hydrogen atom or ahydrocarbon radical having from 1 to 20 carbon atoms, and R₃ and R₄ areas defined above.

[0062] Process Step a1)

[0063] The preparation of iminocarboxylic acid esters of formula II isgenerally known and is described, for example, by L. Weintraub et al. inJ. Org. Chem., Volume 33, No. 4, pages 1679 to 1681 (1968). Theiminocarboxylic acid esters of formula II are advantageously used in theform of salts, for example tetrafluoroborates. In formula II, R₈ may be,for example, methyl, ethyl, n- or iso-propyl or butyl. The reaction canbe carried out at temperatures of from 20 to 150° C. It is advantageousto use solvents such as, for example, halogenated hydrocarbons(methylene chloride, trichloromethane or tetrachloroethane). Equivalentamounts of the reactants are generally used. Serinecarboxylic acidesters of formula III are known. R₉ may be, for example, methyl, ethyl,n- or iso-propyl or butyl.

[0064] Process Step a2)

[0065] The reaction of carboxylic acid esters with metal or metal halidehydrocarbons is known per se. When X₂ is an alkali metal, it may be Na,K or especially Li. In the group Me₁X₃, Me₁ may be, for example, Mg orZn. The reaction is advantageously carried out by adding the compound offormula V at low temperatures, for example from −30 to −80° C., to asolution of the compound of formula IV and then heating the mixture, forexample to room temperature. The reaction can then be completed at thattemperature or at higher temperatures (up to the boiling temperature ofthe solvents used). Suitable solvents are especially ethers, such asdiethyl ether, dibutyl ether, tetrahydrofuran and dioxane.

[0066] Process Step a3)

[0067] The metallation of the compound of formula VI to form metalalcoholates can be carried out with alkali metal alkyls and especiallylithium alkyl, for example lithium methyl, ethyl, propyl or butyl, orwith Grignard reagents, such as methyl-, ethyl-, propyl-, butyl- orbenzyl-magnesium halides. It is advantageous to use equivalent amountsor a slight excess of alkali metal alkyls or Grignard reagents. Theaddition is advantageously made at relatively low temperatures, forexample from −20 to −80° C. The presence of tertiary amines, for exampletrimethyl-, triethyl- or tributyl-amine or tetramethylethylenediaminemay be advantageous. Then at room temperature the reaction can becompleted, the halophosphine of formula VII added and the reaction endedat that temperature. The reaction is preferably carried out in thepresence of inert solvents, for example ethers or hydrocarbons (pentane,hexane, cyclohexane, methylcyclohexane, benzene, toluene or xylene).

[0068] Process Step b1)

[0069] Suitable derivatives of carboxylic acids are esters, amides andespecially halides. The reaction is advantageously carried out in thepresence of solvents, for example halogenated hydrocarbons. Whencarboxylic acids of formula VIII are used, the addition of equimolaramounts of tertiary amines is advantageous, for examplediisopropylethylamine. The presence of at least equimolar amounts ofcarbodiimides is also advantageous. In order to suppress racemisation,the carboxylic acids can be converted into activated esters in thepresence of metal salts, for example copper salts, with selectedalcohols, for example hydroxybenzotriazole. The reaction can be carriedout at temperatures of from −30 to 50° C.

[0070] Process Step b2)

[0071] This reaction can be carried out analogously to Process step a2).

[0072] Process Step b3)

[0073] The reaction is advantageously carried out in the presence of asolvent, for example halogenated hydrocarbons, and at temperatures ofpreferably from 50 to 150° C. A tertiary amine, for exampletriethylamine, and a sulfonic acid halide, such as p-toluenesulfonylchloride, are added to a solution of the compound of formula X and themixture is heated to reflux temperature. The reaction mixture is left toreact for a period of time, water is added and then the reaction mixtureis allowed to react to completion.

[0074] Process Step b4)

[0075] This reaction can be carried out analogously to Process step a3).

[0076] The compounds of formulae Ia and Ib are obtained in good totalyields. By selection of the starting compounds it is possible for thecompounds according to the invention to be synthesised in a modularmanner, the simple starting compounds allowing a large number ofsubstitutions in respect of R₃ and R₄.

[0077] The invention relates also to the intermediates of formulae IV,VI and X obtainable in the process according to the invention.

[0078] The compounds of formulae Ia and Ib according to the inventionare ligands for metal complexes selected from the group of TM8 metals,especially from the group Ru, Rh and Ir, which are excellent catalystsor catalyst precursors for asymmetric syntheses, for example theasymmetric hydrogenation of prochiral, unsaturated, organic compounds.When prochiral unsaturated organic compounds are used, it is possible toinduce a very large excess of optical isomers in the synthesis oforganic compounds and to achieve a high chemical conversion in shortreaction times. The enantioselectivities and catalyst activities thatare achievable are excellent.

[0079] The invention relates also to metal complexes of metals selectedfrom the group of TM8 metals with compounds of formulae I and Ia asligands.

[0080] Examples of metals that come into consideration are Cu, Ag, Au,Ni, Co, Rh, Pd, Ir and Pt. Preferred metals are rhodium and iridium andalso ruthenium, platinum and palladium.

[0081] Especially preferred metals are ruthenium, rhodium and iridium.

[0082] The metal complexes may, according to the oxidation state andcoordination number of the metal atom, contain further ligands and/oranions. They may also be cationic metal complexes. Such analogous metalcomplexes and their preparation are frequently described in theliterature.

[0083] The metal complexes may correspond, for example, to the generalformulae XI and XII,

A₁MeL_(n) (XI), (A₁MeL_(n))^((z+))(E⁻)_(z) (XII),

[0084] wherein A₁ is a compound of formula I or Ia,

[0085] L denotes identical or different, monodentate, anionic ornon-ionic ligands, or two L denote identical or different, bidentate,anionic or non-ionic ligands;

[0086] n is 2, 3 or 4 when L is a monodentate ligand, or n is 1 or 2when L is a bidentate ligand;

[0087] z is 1, 2 or 3;

[0088] Me is a metal selected from the group Rh, Ir and Ru; the metalhaving the oxidation state 0, 1, 2, 3 or 4;

[0089] E⁻ is the anion of an oxyacid or complex acid; and

[0090] the anionic ligands balance the charge of oxidation states 1, 2,3 or 4 of the metal.

[0091] The preferences and embodiments described above apply to thecompounds of formulae I and Ia.

[0092] Monodentate non-ionic ligands may be selected, for example, fromthe group of olefins (for example ethylene, propylene), allyls (allyl,2-methallyl), solvating solvents (nitriles, linear or cyclic ethers,optionally N-alkylated amides and lactams, amines, phosphines, alcohols,carboxylic acid esters, sulfonic acid esters), nitrogen monoxide andcarbon monoxide.

[0093] Monodentate anionic ligands may be selected, for example, fromthe group halide: (F, Cl, Br, I), pseudohalide (cyanide, cyanate,isocyanate) and anions of carboxylic acids, sulfonic acids andphosphonic acids (carbonate, formate, acetate, propionate,methylsulfonate, trifluoromethylsulfonate, phenylsulfonate, tosylate).

[0094] Bidentate non-ionic ligands may be selected, for example, fromthe group of linear or cyclic diolefins (for example hexadiene,cyclooctadiene, norbomadiene), dinitriles (malonic dinitrile),optionally N-alkylated carboxylic acid diamides, diamines, diphosphines,diols, acetonyl acetonates, dicarboxylic acid diesters and disulfonicacid diesters.

[0095] Bidentate anionic ligands may be selected, for example, from thegroup of anions of dicarboxylic acids, disulfonic acids and diphosphonicacids (for example of oxalic acid, malonic acid, succinic acid, maleicacid, methylenedisulfonic acid and methylenediphosphonic acid).

[0096] Preferred metal complexes are also those wherein E is —Cl⁻, —Br⁻,—I⁻, ClO₄ ⁻, CF₃SO₃ ⁻, CH₃SO₃ ⁻, HSO₄ ⁻, (CF₃SO₂)₂N⁻, (CF₃SO₂)₃C⁻,tetraaryl borates, for example B(phenyl)₄ ⁻,B[bis(3,5-trifluoromethyl)phenyl]₄ ⁻, B[bis(3,5-dimethyl)phenyl]₄ ⁻,B(C₆F₅)₄ ⁻ and B(4-methylphenyl)₄ ⁻, BF₄ ⁻, PF₆ ⁻, SbCl₆ ⁻, AsF₆ ⁻ orSbF₆ ⁻.

[0097] Especially preferred metal complexes, which are particularlysuitable for hydrogenations, correspond to formulae XIII and XIV,

[A₁Me₂YZ] (XIII), [A₁Me₂Y]⁺E₁ ⁻ (XIV),

[0098] wherein

[0099] A₁ is a compound of formula I or Ia;

[0100] Me₂ is rhodium or iridium;

[0101] Y denotes two olefins or a diene;

[0102] Z is Cl, Br or I; and

[0103] E₁ ⁻ is the anion of an oxyacid or complex acid.

[0104] The embodiments and preferences described above apply to thecompounds of formulae I and Ia.

[0105] Y as olefin may denote C₂-C₁₂-, preferably C₂-C₆- and moreespecially C₂-C₄-olefin. Examples are propene, but-1-ene and especiallyethylene. The diene may contain from 5 to 12, preferably from 5 to 8,carbon atoms and it may be an open-chain, cyclic or polycyclic diene.The two olefin groups of the diene are preferably bonded by one or twoCH₂ groups. Examples are 1,3-pentadiene, cyclopentadiene, 1,5-hexadiene,1,4-cyclohexadiene, 1,4- or 1,5-heptadiene, 1,4- or 1,5-cycloheptadiene,1,4- or 1,5-octadiene, 1,4- or 1,5-cyclooctadiene and norbornadiene. Ypreferably denotes two ethylene or 1,5-hexadiene, 1,5-cyclooctadiene ornorbornadiene.

[0106] In formula XIII, Z is preferably Cl or Br. Examples of E₁ are BF₄⁻, ClO₄ ⁻, CF₃SO₃ ⁻, CH₃SO₃ ⁻, HSO₄ ⁻, B(phenyl)₄ ⁻,B[bis(3,5-trifluoromethyl)phenyl]₄ ⁻, PF₆ ⁻, SbCl₆ ⁻, AsF₆ ⁻ and SbF₆ ⁻.

[0107] The metal complexes according to the invention are prepared inaccordance with methods known in the literature (see also U.S. Pat. Nos.5,371,256, 5,446,844, 5,583,241, and E. Jacobsen, A. Pfaltz, H. Yamamoto(Eds.), Comprehensive Asymmetric Catalysis I to III, Springer Verlag,Berlin, 1999, and literature referred to therein).

[0108] The metal complexes according to the invention are homogeneouscatalysts, or catalyst precursors capable of being activated under thereaction conditions, which can be used for asymmetric addition reactionswith prochiral, unsaturated, organic compounds.

[0109] The metal complexes can be used, for example, for the asymmetrichydrogenation (addition of hydrogen) of prochiral compounds havingcarbon-carbon or carbon-hetero atom multiple bonds, especially doublebonds. Such hydrogenations with soluble homogeneous metal complexes aredescribed, for example, in Pure and Appl. Chem., Vol. 68, No. 1, pp.131-138 (1996). Preferred unsaturated compounds to be hydrogenatedcontain the groups C═C, C═N and/or C═O. For the hydrogenation the use ofmetal complexes of rhodium and iridium is preferred according to theinvention.

[0110] The metal complexes according to the invention can also be usedas catalysts in the asymmetric hydroboration (addition of borohydrides)of prochiral organic compounds having carbon-carbon double bonds. Suchhydroborations are described, for example, by Tamio Hayashi in E.Jacobsen, A. Pfaltz, H. Yamamoto (Eds.), Comprehensive AsymmetricCatalysis I to III, Springer Verlag, Berlin, 1999, pages 351 to 364.Suitable borohydrides are, for example, catechol boranes. The chiralboron compounds can be used in syntheses and/or reacted in a mannerknown per se to form other chiral organic compounds that are valuablebuilding blocks for the preparation of chiral intermediates or activeingredients. One example of such a reaction is the preparation of3-hydroxy-tetrahydrofuran (according to DE 198 07 330).

[0111] The metal complexes according to the invention can also be usedas catalysts in the asymmetric hydrosilylation (addition of silanes) ofprochiral organic compounds having carbon-carbon or carbon-hetero atomdouble bonds. Such hydrosilylations are described, for example, by G.Pioda and A. Togni in Tetrahedron: Asymmetry, 1998, 9, 3093 or by S.Uemura, et at. in Chem. Commun. 1996, 847. Suitable silanes are, forexample, trichlorosilane or diphenylsilane. For the hydrosilylation of,for example, C═O and C═N groups it is preferable to use metal complexesof rhodium and iridium. For the hydrosilylation of, for example, C═Cgroups it is preferable to use metal complexes of palladium. The chiralsilyl compounds can be used in syntheses and/or reacted in a mannerknown per se to form other chiral organic compounds that are valuablebuilding blocks for the preparation of chiral intermediates or activeingredients. Examples of such reactions are hydrolysis to alcohols.

[0112] The metal complexes according to the invention can also be usedas catalysts for asymmetric allylic substitution reactions (addition ofC-nucleophiles to allyl compounds). Such aminations are described, forexample, by A. Pfaltz and M. Lautens in E. Jacobsen, A. Pfaltz, H.Yamamoto (Eds.), Comprehensive Asymmetric Catalysis I to III, SpringerVerlag, Berlin, 1999, pages 833 to 884. Suitable precursors for allylcompounds are, for example, 1,3-diphenyl-3-acetoxy-1-propene and3-acetoxy-1-cyclohexene. For that reaction it is preferable to use metalcomplexes of palladium. The chiral allyl compounds can be used insyntheses for the preparation of chiral intermediates or activeingredients.

[0113] The metal complexes according to the invention can also be usedas catalysts in asymmetric amination (addition of amines to allylcompounds) or in asymmetric Heck reactions. Such aminations aredescribed, for example, by A. Pfaltz and M. Lautens in E. Jacobsen, A.Pfaltz, H. Yamamoto (Eds.), Comprehensive Asymmetric Catalysis I to III,Springer Verlag, Berlin, 1999, pages 833 to 884, and Heck reactions byO. Loiseleur et al. in Journal of Organometallic Chemistry 576 (1999),pages 16 to 22. Suitable amines, in addition to ammonia, are primary andsecondary amines. For the amination of allyl compounds it is preferableto use metal complexes of palladium. The chiral amines can be used insyntheses for the preparation of chiral intermediates or activeingredients.

[0114] The invention relates also to the use of the metal complexesaccording to the invention as homogeneous catalysts in the preparationof chiral organic compounds by asymmetric addition of hydrogen,borohydrides or silanes to a carbon-carbon or carbon-hetero atommultiple bond in prochiral organic compounds or asymmetric addition ofC-nucleophiles or amines to allyl compounds.

[0115] The invention relates further to a process for the preparation ofchiral organic compounds by asymmetric addition of hydrogen,borohydrides or silanes to a carbon-carbon or carbonhetero atom multiplebond in prochiral organic compounds or asymmetric addition ofC-nucleophiles or amines to allyl compounds in the presence of acatalyst, wherein the addition is carried out in the presence ofcatalytic amounts of at least one metal complex according to theinvention.

[0116] Preferred prochiral unsaturated compounds to be hydrogenated maycontain one or more, identical or different groups C═C, C═N and/or C═Oin open-chain or cyclic organic compounds, the groups C═C, C═N and/orC═O being part of a ring system or being exocyclic groups. The prochiralunsaturated compounds may be alkenes, cycloalkenes andheterocycloalkenes, and also open-chain or cyclic ketones, ketimines andketohydrazones. They may correspond, for example, to formula X,

R₀₇R₀₈C═D  (XVIII),

[0117] wherein R₀₇ and R₀₈ are so selected that the compound isprochiral and are each independently of the other an open-chain orcyclic hydrocarbon radical or heterohydrocarbon radical having heteroatoms selected from the group O, S and N, that contains from 1 to 30,preferably from 1 to 20, carbon atoms;

[0118] D is O or a radical of formula C═R₀₉R₁₀ or NR₁₁;

[0119] R₀₉ and R₁₀ each independently of the other have the samemeanings as R₀₇ and R₀₈, R₁₁ is hydrogen, C₁-C₁₂alkyl, C₁-C₁₂alkoxy,C₃-C₁₂cycloalkyl, C₃-C₁₂cycloalkyl-C₁-C₆alkyl, C₃-C₁₁heterocycloalkyl,C₃-C₁₁heterocycloalkyl-C₁-C₆alkyl, C₆-C₁₄aryl, C₅-C₁₃heteroaryl,C₇-C₁₆aralkyl or C₆-C₁₄heteroaralkyl,

[0120] R₀₇ and R₀₈ together with the carbon atom to which they arebonded form a hydrocarbon ring or heterohydrocarbon ring having from 3to 12 ring members;

[0121] R₀₇ and R₀₈ each together with the C═C group to which they arebonded form a hydrocarbon ring or heterohydrocarbon ring having from 3to 12 ring members;

[0122] R₀₇ and R₁₁ each together with the C═N group to which they arebonded form a hydrocarbon ring or heterohydrocarbon ring having from 3to 12 ring members;

[0123] the hetero atoms in the heterocyclic rings being selected fromthe group O, S and N;

[0124] and R₀₇, R₀₈, R₀₉, R₁₀ and R₁₁ are unsubstituted or substitutedby C₁-C₆alkyl, C₁-C₆alkoxy, cyclohexyl, C₆-C₁₀aryl, C₇-C₁₂aralkyl,C₁-C₄alkyl-C₆-C₁₀aryl, C₁-C₄alkoxy-C₆-C₁₀aryl,C₁-C₄-alkyl-C₇-C₁₂aralkyl, C₁-C₄alkoxy-C₇C₁₂aralkyl, —OH, ═O, —CO—OR₁₂,—CO—NR₁₃R₁₄ or by —NR₁₃R₁₄, wherein R₁₂ is H, an alkali metal,C₁-C₆alkyl, cyclohexyl, phenyl or benzyl, and R₁₃ and R₁₄ are eachindependently of the other hydrogen, C₁-C₆alkyl, cyclohexyl, phenyl orbenzyl, or R₁₃ and R₁₄ together are tetramethylene, pentamethylene or3-oxapentylene.

[0125] Examples and preferences for substituents have been given above.

[0126] R₀₇ and R₀₈ may be, for example, C₁-C₂₀alkyl and preferablyC₁-C₁₂alkyl, C₁-C₂₀heteroalkyl and preferably C₁-C₁₂heteroalkyl havinghetero atoms selected from the group O, S and N, C₃-C₁₂cycloalkyl andpreferably C₄-C₈cycloalkyl, C-bonded C₃-C₁₁heterocycloalkyl andpreferably C₄-C₈heterocycloalkyl having hetero atoms selected from thegroup O, S and N, C₃-C₁₂cycloalkyl-C₁-C₆alkyl and preferablyC₄-C₈cycloalkyl-C₁-C₆alkyl, C₃-C₁₁heterocycloalkyl-C₁-C₆alkyl andpreferably C₄-C₈heterocycloalkyl-C₁-C₆alkyl having hetero atoms selectedfrom the group O, S and N, C₆-C₁₄aryl and preferably C₆-C₁₀aryl,C₅-C₁₃heteroaryl and preferably C₅-C₉heteroaryl having hetero atomsselected from the group O, S and N, C₇-C₁₅aralkyl and preferablyC₇-C₁₁aralkyl, C₆-C₁₂heteroaralkyl and preferably C₆-C₁₀heteroaralkylhaving hetero atoms selected from the group O, S and N.

[0127] When R₀₇ and R₀₈, R₀₇ and R₀₉, or R₀₇ and R₁₁, in each casetogether with the group to which they are bonded, form a hydrocarbonring or heterohydrocarbon ring, that ring preferably contains from 4 to8 ring members. The heterohydrocarbon ring may contain, for example,from 1 to 3, preferably one or two, hetero atoms.

[0128] R₁₁ is preferably hydrogen, C₁-C₆alkyl, C₁-C₆alkoxy,C₄-C₈cycloalkyl, C₄-C₈cycloalkyl-C₁-C₄alkyl, C₄-C₁₀heterocycloalkyl,C₄-C₁₀heterocycloalkyl-C₁-C₄alkyl, C₆-C₁₀aryl, C₅-C₉heteroaryl,C₇-C₁₂aralkyl or C₅-C₁₃heteroaralkyl.

[0129] Some examples of unsaturated organic compounds are acetophenone,4-methoxyacetophenone, 4-trifluoromethylacetophenone,4-nitroacetophenone, 2-chloroacetophenone, corresponding unsubstitutedor N-substituted acetophenonebenzylimines, unsubstituted or substitutedbenzocyclohexanone or benzocyclopentanone and corresponding imines,imines from the group of unsubstituted or substitutedtetrahydroquinoline, tetrahydropyridine and dihydropyrrole, andunsaturated carboxylic acids, esters, amides and salts, for example α-and optionally β-substituted acrylic acids or crotonic acids. Preferredcarboxylic acids are those of the formula

R₁₂—CH═C(R₁₃)—C(O)OH

[0130] and their salts, esters and amides, wherein R₁₂ is C₁-C₆alkyl;C₃-C₈cycloalkyl unsubstituted or substituted by from 1 to 4 C₁-C₆alkyl,C₁-C₆alkoxy or C₁-C₆alkoxy-C₁-C₄alkoxy substituents, or C₆-C₁₀aryl,preferably phenyl, unsubstituted or substituted by from 1 to 4C₁-C₆alkyl, C₁-C₆alkoxy or C₁-C₆alkoxy-C₁-C₄alkoxy substituents; and R₁₃is linear or branched C₁-C₆-alkyl (for example isopropyl) or,unsubstituted or substituted as defined above, cyclopentyl, cyclohexyl,phenyl or protected amino (for example acetylamino).

[0131] The process according to the invention can be carried out at lowor elevated temperatures, for example from −20 to 150° C., preferablyfrom −10 to 100° C., more especially from 10 to 80° C. The opticalyields are generally better at lower temperature than at highertemperatures.

[0132] The process according to the invention can be carried out atnormal pressure or excess pressure. The pressure may be, for example,from 10⁵ to 2×10⁷ Pa (Pascal). Hydrogenations can be carried out atnormal pressure or at excess pressure. Better selectivities are oftenobserved at normal pressure.

[0133] Catalysts are used preferably in amounts of from 0.0001 to 10 mol%, especially from 0.001 to 10 mol %, more especially from 0.01 to 5 mol%, based on the compound to be hydrogenated.

[0134] The preparation of the ligands and catalysts and also theaddition reaction can be carried out without a solvent or in thepresence of an inert solvent, it being possible to use one solvent or amixture of solvents. Examples of suitable solvents are aliphatic,cycloaliphatic and aromatic hydrocarbons (pentane, hexane, petroleumether, cyclohexane, methylcyclohexane, benzene, toluene, xylene),aliphatic halogenated hydrocarbons (methylene chloride, chloroform, di-and tetra-chloroethane), nitriles (acetonitrile, propionitrile,benzonitrile), ethers (diethyl ether, dibutyl ether, tert-butyl methylether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether,diethylene glycol dimethyl ether, tetrahydrofuran, dioxane, diethyleneglycol monomethyl or monoethyl ether), ketones (acetone, methyl isobutylketone), carboxylic acid esters and lactones (ethyl or methyl acetate,valerolactone), N-substituted lactams (N-methylpyrrolidone), carboxylicacid amides (dimethylamide, dimethylformamide), acyclic ureas(dimethylimidazoline), and sulfoxides and sulfones (dimethyl sulfoxide,dimethyl sulfone, tetramethylene sulfoxide, tetramethylene sulfone) andalcohols (methanol, ethanol, propanol, butanol, ethylene glycolmonomethyl ether, ethylene glycol monoethyl ether, diethylene glycolmonomethyl ether) and water. The solvents can be used on their own or ina mixture of at least two solvents.

[0135] The reaction can be carried out in the presence of co-catalysts,for example quaternary ammonium halides (tetrabutylammonium iodide)and/or in the presence of protonic acids, for example mineral acids(see, for example, U.S. Pat. Nos. 5,371,256, 5,446,844 and 5,583,241 andEP-A-0 691 949). The co-catalysts are especially suitable forhydrogenations.

[0136] The metal complexes used as catalysts can be added in the form ofseparately prepared isolated compounds or alternatively they can beformed in situ prior to the reaction and then mixed with the substrateto be hydrogenated. It may be advantageous, when isolated metalcomplexes are being used in the reaction, additionally to add ligandsor, in the case of in situ preparation, to use the ligands in excess.The excess may be, for example, from 1 to 10 mol, preferably from 1 to 5mol, based on the metal compound used for preparation.

[0137] The process according to the invention is generally carried outby first introducing the catalyst into the reaction vessel and thenadding the substrate, optionally reaction auxiliaries and the additionreaction compound and subsequently starting the reaction. Compounds tobe added that are in gaseous form, for example hydrogen or ammonia, arepreferably introduced under pressure. The process can be carried outcontinously or intermittently in various types of reactor.

[0138] The chiral organic compounds that can be prepared according tothe invention are active ingredients or intermediates in the preparationof such ingredients, especially in the field of the manufacture ofpharmaceuticals and agrochemicals. For example, o,o-dialkyl arylketaminederivatives, especially those having alkyl and/or alkoxyalkyl groups,are effective as fungicides, especially as herbicides. The derivativesmay be amine salts, acid amides, for example of choroacetic acid,tertiary amines and ammonium salts (see e.g. EP-A-0 077 755 and EP-A-0115 470).

[0139] The following Examples illustrate the invention. Chromatographicseparation and purification is carried out using C-Gel C-560 (UetikonAG, Switzerland).

A) PREPARATION OF INTERMEDIATES Example A1

[0140] Preparation of

[0141] a) Preparation of(−)-N-(1-carboxymethyl-2-hydroxy-ethyl)-3,5-di-tert-butylbenzamide (A1a)

[0142] 2.53 g (16.3 mmol) of D-serine methyl ester hydrochloride aresuspended in 50 ml of dichloromethane, and at 0° C. 2.23 g (16.3 mmol)of diisopropylethylamine and 3.81 g (16.3 mmol) of3,5-di-tert-butylbenzoic acid are added in succession thereto. After theaddition of 3.7 g (19.6 mmol) ofN-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride (EDC), ahomogeneous yellow solution is formed which is stirred at roomtemperature (RT) for 3 h. Extraction is then carried out with water andNH₄Cl solution (each 3×25 ml), the organic phase is dried over MgSO₄ andafter column chromatography (15×4 cm, hexane/ethyl acetate 3:2) 5.4 g(99% of theory) of a colourless solid are obtained.

[0143]¹H-NMR (400 MHz, CDCl₃): 1.35 (s, 18H, CH₃—C); 3.84 (s, 3H,CH₃—O); 4.08 (dd, J=6.06/3.79, 2H, CH₂—O); 4.88 (dt, J=6.82/3.79, 1H,CH—N); 7.05 (d, J=6.82, 1H, NH); 7.60 (t, J=1.76, 1H, Ar—H); 7.63 (d,J=1.76, 1H, Ar—H).

[0144]¹³C-NMR (100 MHz, CDCl₃): 31.7 (6C, CH₃); 35.3 (2C, Cq—C); 53.2(1C, CH₃—O); 55.7 (1C, CH₂—N); 64.2 (1C, CH₂—O); 121.6 (2C, Ar—H); 126.6(1C, Ar—H); 133.5 (1C, Ar—C═O); 151.8 (2C, Ar—CCH₃). α_(D) (25° C.,CHCl₃, c=1.0)=−30.5.

[0145] b) Preparation of(−)-N-(2-hydroxy-1-hydroxymethyl-3-isobutyl)-3,5-di-tert-butylbenzamide(A1b)

[0146] 1.62 g (4.8 mmol) of compound A1a are dissolved in 20 ml ofdiethyl ether and cooled to −78° C., and 10 ml (20 mmol) of 2Misobutylmagnesium chloride solution in diethyl ether are slowly addedthereto. Stirring is carried out at RT for 12 h, NH₄Cl solution is addedat 0° C., the aqueous phase is extracted with diethyl ether (3×10 ml)and the combined organic phases are dried over MgSO₄. Columnchromatography (15×3 cm, hexane/ethyl acetate 2:1) yields 664 mg (33%)of white solid.

[0147]¹H-NMR (300 MHz, CDCl₃): 0.93 (d, J=6.6, 3H, CH₃); 0.99 (d, J=6.5,3H, CH₃); 1.01 (d, J=6.6, 3H, CH₃); 1.06 (d, J=6.4, 3H, CH₃); 1.35 (s,18H, CH₃); 1.59 (d, J=5.8, 2H, CH₂); 1.60 (s, 1H, OH); 1.65 (d, J=6.0,2H, CH₂); 1.75 (quint, J=6.5, 1H, CH); 1.87 (quint, J=6.3, 1H, CH); 2.73(sbr, 1H, OH); 3.98-4.16 (m, 3H, Ox—H): 7.07 (d, J=7.6, 1H, NH); 7.59(t, J=1.8, 1H, Ar—H); 7.64 (d,J=1.8, 2H, Ar—H).

[0148]¹³C-NMR (75 MHz, CDCl₃): 23.9 (1C, CH₃); 24.1 (1C, CH₃); 24.3 (1C,CH₃); 24.4 (1C, CH₃); 24.8 (1C, CH); 25.1 (1C, CH); 31.3 (6C, CH₃); 34.9(2C, Cq); 44.6 (1C, CH₂); 45.6 (1C, CH₂); 55.7 (1C, CH—N); 63.4 (1C,CH₂—O); 78.3 (1C, Cq—O); 121.1 (2C, Ar—H); 125.8 (1C, Ar—H); 134.1 (1C,Ar—C═C); 151.1 (2C, Ar—C—C); 168.7 (1C, C═N); 211.2 (1C, C═O).

[0149] c) Preparation of Title Compound A1

[0150] 664 mg (1.58 mmol) of compound A1b 16 are dissolved in 10 ml ofdichloromethane, and heated at reflux for 4 h with 2 ml of triethylamineand 386 mg (2.0 mmol) of p-toluenesulfonyl chloride. After the additionof 2 ml of water, the reaction mixture is again heated at reflux for 2h, extracted with NH₄Cl solution (3×5 ml) and dried over MgSO₄. Columnchromatography (15×2 cm, hexane/ethyl acetate 7:1) yields 358 mg (56% oftheory) of a colourless amorphous solid.

Example A2

[0151] Preparation of

[0152] a) Preparation of(+)-N-(1-carboxymethyl-2-hydroxy)ethylbiphenylcarbamide (A2a)

[0153] Preparation is carried out analogously to Example A1a usingL-serine methyl ester hydrochloride and 1,1′-biphenyl-4-carboxylic acid.1.6 g (36% of theory) of a colourless solid are obtained.

[0154]¹H-NMR (300 MHz, CDCl₃): 0.91 (d, J=6.5, 3H, CH₃); 0.98 (d, J=6.5,3H, CH₃); 1.00 (d, J=7.5, 3H, CH₃); 1.06 (d, J=6.5, 3H, CH₃); 1.58 (d,J=6.5, 2H, CH₂); 1.66 (d, J=6.0, 2H, CH₂); 1.68-1.77 (m, 1H, CH);1.80-1.91 (m, 1H, CH); 4.07-4.17 (m, 3H, CH₂O, CHN); 7.14 (d, J=9; 1H,NH); 7.38-7.49 (m, 3H, ArH); 7.59-7.68 (m, 4H, ArH); 7.88-7.91 (m, 2H,ArH).

[0155]¹³C-NMR (75 MHz, CDCl₃): 24.0, 24.3, 24.8, 25.1 (6C, CH₃, CH);31.3 (2C, CH₂); 55.3 (CH₂O); 76.8 (CHN); 79.3 (qC); 127.2-128.9(aromatic C); 211 (C═O). α_(D)(25° C., c=0.64, CHCl₃)=+46.8.

[0156] b) Preparation of(+)-N-(2-hydroxy-1-hydroxymethyl-2-isobutyl-3-methyl)pentyl-biphenylcarbamide

[0157] Preparation is carried out analogously to Example A1b. Columnchromatography (15×3 cm, hexane/ethyl acetate 3:1) gives a yield of 43%.

[0158]¹H-NMR (300 MHz, CDCl₃): 0.91 (d, J=6.5, 3H, CH₃); 0.98 (d, J=6.5,3H, CH₃); 1.00 (d, J=7.5, 3H, CH₃); 1.06 (d, J=6.5, 3H, CH₃); 1.58 (d,J=6.5, 2H, CH₂); 1.66 (d, J=6.0, 2H, CH₂); 1.68-1.77 (m, 1H, CH);1.80-1.91 (m, 1H, CH); 4.07-4.17 (m, 3H, CH₂O, CHN); 7.14 (d, J=9; 1 H,NH); 7.38-7.49 (m, 3H, ArH); 7.59-7.68 (m, 4H, ArH); 7.88-7.91 (m, 2H,ArH).

[0159]¹³C-NMR (75 MHz, CDCl₃): 24.0, 24.3, 24.8, 25.1 (6C, CH₃, CH);31.3 (2C, CH₂); 55.3 (CH₂O); 76.8 (CHN); 79.3 (qC); 127.2-128.9(aromatic C); 211 (C═O).

[0160] c) Preparation of the Title Compound

[0161] Preparation is carried out analogously to Example A1c. 89 mg (43%of theory) of a colourless oil are obtained.

[0162]¹H-NMR (300 MHz, CDCl₃): 0.87 (d, J=6.6, 3H, CH₃); 0.93 (d, J=6.5,3H, CH₃); 0.95 (d, J=6.5, 3H, CH₃); 0.96 (d, J=6.6, 3H, CH₃); 1.21 (dd,J=14.7/5.5, 1H, CH₂); 1.38 (dd, J=14.5/6.6, 1H, CH₂); 1.47 (s, 1H, OH);1.56 (dd, J=14.7/7.1, 1H, CH₂); 1.66 (dd, J=14.5/5.1, 1H, CH₂);1.71-1.86 (m, 2H, CH); 4.28-4.37 (m, 3H, Ox—H); 7.31-7.42 (m, 3H, Ar—H);7.53-7.59 (m, 4H, Ar—H); 7.94-7.97 (m, 2H, Ar—H).

[0163]¹³C-NMR (100 MHz, CDCl₃): 24.2, 24.4, 24.9 (3C, CH₃); 25.2, 25.3(CH); 44.2, 46.1 (CH₂); 69.0 (CH₂O); 74.6 (CHN); 76.5 (qC); 127-129(aromatic C).

Example A3

[0164] Preparation of

[0165] a) Preparation of1-{N-(1-carboxymethyl-2-hydroxy)}naphthylcarbamide

[0166] 3 g (19.6 mmol) of L-serine methyl ester hydrochloride aredissolved in 100 ml of water and cooled to 0° C., and 3.1 g of NaHCO₃are added thereto. After the addition of 3.7 g (19.5 mmol) of1-naphthylcarbonyl chloride, stirring is carried out at RT for 72 hours.The aqueous suspension is extracted with chloroform and the organicextracts are dried over MgSO₄. After column chromatography (15×3 cm,hexane/ethyl acetate 1:1), 565 mg (11% of theory) of a colourless oilare obtained.

[0167]¹H-NMR (300 MHz, CDCl₃): 2.80 (sbr, 1H, OH); 3.95 (dd, J=11.1/3.4,1H, CH₂O); 4.02 (dd, J=11.1/3.7, 1H, CH₂O); 4.85 (dt, J=7.7/3.7, 1H,CHN); 6.92 (d, J=7.35, 1H, NH); 7.34 (dd, J=7.1/8.25, 1H, ArH);7.43-7.48 (m, 2H, ArH); 7.59 (dd, J=7.01/1.2, 1H, ArH); 7.76-7.85 (m,2H, ArH); 8.26 (d, J=8.1, 1H, ArH).

[0168]¹³C-NMR (75 MHz, CDCl₃): 52.8 (1C, OCH₃); 55.0 (1C, OCH₂); 63.2(1C, NCH); 124.6 (C3); 125.2 (C5); 126.4 (C9); 127.2 (C8); 128.3 (C10);130.0 (C6); 131.0 (C7); 133.2 (C2); 133.6 (C₁); 169.8 (NC═O); 170.8(OC═O).

[0169] b) Preparation of1-(N-(2-hydroxy-1-hydroxymethyl-2-isobutyl-methyl)pentyl)-naphthylcarbamide

[0170] Preparation is carried out analogously to Example A1b. Columnchromatography (15×2 cm, hexane/ethyl acetate 2:1) yields 661 mg (91%).

[0171]¹H-NMR (300 MHz, CDCl₃): 0.88 (d, J=6.5, 6H, CH₃); 0.90 (d, J=6.5,3H, CH₃); 0.94 (d, J=6.5, 3H, CH₃); 1.48-1.53 (m, 4H, CH₂); 1.58-1.80(m, 2H, CH); 2.81 (s, 1H, OH); 3.01 (s, 1H, OH); 3.90-4.07 (m, 3H,Ox—H); 6.89 (d, J=8.4, 1H, NH); 7.29 (dd, J=7.0/8.2, 1H, ArH); 7.41-7.45(m, 2H, ArH); 7.51 (dd, J=7.0/1.2, 1H, ArH); 7.75-7.81 (m, 2H, ArH);8.22-8.25 (m, 1H, ArH).

[0172]¹³C-NMR (75 MHz, CDCl₃): 23.9 (1C, CH₃); 24.0 (1C, CH); 24.3 (2C,CH₃ ); 24.8 (1C, CH₃); 25.0 (1C, CH); 44.4 (1C, CH₂); 45.2 (1C, CH₂);55.3 (1C, CHN); 63.3 (1C, OCH₂); 78.3 (1C, qC); 124.6, 124.9, 125.3,126.4, 127.1, 128.2 (1C, ArH); 130.1 (1C, ArC); 130.6 (1C, ArH); 133.6,134.2 (1C, ArC); 169.7 (C═O).

[0173] c) Preparation of the Title Compound

[0174] Preparation is carried out analogously to Example A1c. Columnchromatography (15×2 cm, hexanelethyl acetate 4:1) yields 134 mg (62%).

[0175]¹H-NMR (300 MHz, CDCl₃): 0.90 (d, J=6.6, 3H, CH₃); 0.96 (d, J=6.6,3H, CH₃); 0.97 (d, J=6.5, 3H, CH₃); 1.00 (d, J=6.6, 3H, CH₃); 1.29 (dd,J=14.5/5.4, 1H, CH₂); 1.42 (dd, J=14.5/6.8, 1H, CH₂); 1.47 (s, 1H, OH);1.62 (dd, J=14.5/6.8, 1H, CH₂); 1.72 (dd, J=14.5/5.2, 1H, CH₂); 1.83(hept, J=6.5, 2H, CH); 4.30-4.40 (m, 2H, OCH₂); 4.51 (overlapping, dd,J=9.5, 1H, CHN); 7.40-7.56 (m, 3H, ArH); 7.81 (dd, J=7.9/6.2, 1H, ArH);7.89 (d, J=8.2, 1H, ArH); 8.02 (dd, J=7.2/6.0, 1H, ArH); 9.07 (d, J=8.5,1H, ArH).

[0176]^(—C-NMR ()100 MHz, CDCl₃): 24.2, 25.5 (CH₃); 24.9 (CH); 25.0(CH₃); 25.3 (CH); 25.4 (CH₃); 44.4 (CH₂); 46.2 (CH₂); 67.9 (CH₂O); 75.3(CHN); 76.6 (qC); 124.8, 125.0, 126.4, 126.8 127.7, 128.9, 129.5(NaphH); 131.6, 132.4, 134.1 (NaphC); 165.1 (C═N).

Example A4

[0177] Preparation of

[0178] a) Preparation of 2-tert-butyl-4-carboxymethyl-oxazoline (A4a)

[0179] 3 g (29.6 mmol) of pivalic acid amide are stirred with 5.6 g(29.6 mmol) of triethyloxonium tetrafluoroborate in 50 ml ofdichloromethane for 48 h. Ammonia is passed through the solution over aperiod of 3 h, the resulting residue is filtered off and the filtrate isconcentrated in a rotary evaporator. 4.67 g (30 mmol) of L-serine methylester hydrochloride are added with 50 ml of dichloroethane, and themixture is then heated at reflux for 8 h. Extraction with NaHCO₃solution and NH₄Cl solution, drying over MgSO₄ and purification bycolumn chromatography (15×3 cm, pentane/diethyl ether 4:1) are carriedout. Yield 1.34 g (24% of theory).

[0180]¹H-NMR (300 MHz, CDCl₃): 1.24 (s, 9H, CH₃); 3.78 (s, 3H, OCH₃);4.37 (dd, J=8.7/10.5, 1H, CH₂O); 4.46 (dd, J=8.7/7.6, 1H, CH₂O); 4.71(dd, J=10.5/7.6, 1H, CHN).

[0181]¹³C-NMR (75 MHz, CDCl₃): 27.7 (3C, CH₃); 33.3 (1C, qC); 52.5 (1C,OCH₃); 68.1 (1C, OCH₂); 69.4 (1C, CHN); 176.9 (1C, C═O).

[0182] b) Preparation of A4

[0183] 676 mg (3.6 mmol) of oxazoline A4a are dissolved in 10 ml ofdiethyl ether and cooled to −78° C., and 9 ml of 1M benzylmagnesiumchloride solution in diethyl ether are added thereto. The mixture isstirred at room temperature (RT) for 60 h, extracted with NH₄Cl solutionand dried over MgSO₄. Column chromatography (15×3 cm, pentane/diethylether 4:1) yields 1.2 g of A1 (98% of theory).

[0184]¹H-NMR (300 MHz, CDCl₃): 1.16 (s, 9H, CH₃); 2.52 (d, J=13.7, 1H,CH₂Ar); 2.68 (s, 2H, CH₂Ar); 2.80 (d, J=13.7, 1H, CH₂Ar); 3.94-3.97 (m,2H, CH₂O); 4.09 (dd, J=4.3/5.2, 1H, CHN); 7.15-7.29 (m, 10H, ArH).

[0185]¹³C-NMR (75 MHz, CDCl₃): 27.9 (3C, CH₃); 41.6 (1C, CH₂Ar); 41.9(1C, CH₂Ar); 68.3 (1C, CH₂O); 71.6 (1C, CHN); 75.6 (1C, qC); 126.4 (4C,ArH); 128.1 (4C, ArH); 130.8 (1C, ArH); 130.9 (1C, ArH); 136.9 (1C,ArC); 137.0 (ArC).

Example A5

[0186] Preparation of

[0187] a) Preparation of 2-phenyl-4-carboxymethyloxazoline (A5a)

[0188] 567 mg (3.6 mmol) of L-serine methyl ester hydrochloride aredissolved in 0.5 ml of water, and 610 mg (3.6 mmol) of ethyl benzimidatein 10 ml of dichloromethane are added thereto. After 48 h at reflux, themixture is concentrated to a volume of 50 ml of dichloromethane andwashed with NaHCO₃ (3×10 ml), and the aqueous phase is extracted withethyl acetate (2×10 ml). Column chromatography (15×5 cm, hexane/ethylacetate 1:1) yields 3.0 g of A2a (91% of theory).

[0189]¹H-NMR (300 MHz, CDCl₃): 3.78 (s, 3H, OCH₃); 4.52-4.69 (m, 2H,CH₂O); 4.89-4.93 (m, 1H, CHN); 7.35-7.49 (m, 3H, ArH); 7.94-7.97 (m, 2H,ArH).

[0190]¹³C-NMR (75 MHz, CDCl₃): 53.0 (OCH₃); 68.5 (CH₂O); 69.7 (CHN);128.7, 128.9, 132.2 (ArH); 166.6 (C═N); 171.9 (C═O).

[0191] b) Preparation of A5

[0192] Preparation is carried out analogously to Example A4b usingisopropylmagnesium chloride and compound A5a. Column chromatography(15×3 cm, hexane/ethyl acetate 6:1) yields 300 mg (20% of theory).

[0193]¹H-NMR (400 MHz, CDCl₃): 0.94 (d, J=6.8, 3H, CH₃); 0.97 (d, J=6.8,3H, CH₃); 0.99 (d, J=7.1, 3H, CH₃); 1.11 (d, J=7.1, 3H, CH₃); 1.95-2.04(m, 1H, CH); 2.20-2.20 (m, 2H, CH, OH); 4.41 (dd, J=10.2/8.4, 2H, CH₂O);4.62 (t, J=10.2, 1H, CHN); 7.25-7.50 (m, 3H, ArH); 7.93-7.98 (m, 2H,ArH).

[0194]¹³C-NMR (100 MHz, CDCl₃): 18.3, 18.5, 18.7, 18.7 (CH₃); 32.8, 33.9(CH); 69.4 (CH₂O); 70.7 (CHN); 77.7 (qC); 128.1 (ArC); 128.6, 131.7(ArH); 164.1 (C═N).

Example A6

[0195] Preparation of

[0196] Title compound A6 is prepared analogously to Example A4b usingcompound A5a and benzylmagnesium chloride.

Example A7

[0197] Preparation of

[0198] a) Preparation of 2-(1-fluorophenyl)-4-carboxymethyloxazoline(A5a)

[0199] 878 mg (6.31 mmol) of 2-fluorobenzamide are stirred at RT with1.2 g (6.31 mmol) of triethyloxonium tetrafluoroborate in 50 ml ofdichloroethane. The precipitated solid is filtered off, washed withdiethyl ether, dissolved in 50 ml of NaHCO₃ solution, and the aqueoussolution is extracted with dichloroethane (5×20 ml). After the additionof 980 mg of D-serine methyl ester hydrochloride, the mixture is heatedat reflux for 60 hours, filtered when cold and washed with NaClsolution. Column chromatography (15×3 cm, hexane/ethyl acetate 1:1)yields 1.08 g (71% of theory) of A7a.

[0200]¹H-NMR (200 MHz, CDCl₃): 3.81 (s, 3H, OCH₃); 4.50-4.72 (m, 2H,CH₂O); 4.99 (dd, J=7.9/2.8, 1H, NCH); 7.10- 7.22 (m, 2H, ArH); 7.43-7.53(m, 1H, ArH); 7.93 (dt, J=8/1.9, 1H, ArH).

[0201]¹³C-NMR (50 MHz, CDCl₃): 52.3 (OCH₃); 68.2 (OCH₂); 69.0 (CHN);116.3 (d, J_(CF)=21.8, ArH); 123.6 (d, J_(CF)=3.6, ArH); 131.0 (ArH);133.1 (d, J_(CF)=8.7, ArH); 160.9 (d, J_(CF)=259, ArF); 171.0 (ArC).

[0202] b) Preparation of Compound A7

[0203] Preparation is carried out analogously to Example A4b usingcompound A7a and benzylmagnesium chloride. Column chromatography (15×2cm, hexaneltert-butyl methyl ether 4:1) yields 264 mg of A7 (29% oftheory).

[0204]¹H-NMR (200 MHz, CDCl₃): 2.01 (sbr, 1H, OH); 2.69 (d, J=13.7, 1H,CH₂Ar); 2.88 (s, 2H, CH₂Ar); 3.00 (d, J=13.7, 1H, CH₂Ar); 4.18-4.39 (m,3H, CH₂O, CHN); 7.22-7.31 (m, 12 H, ArH); 7.40-7.51 (m, 1H ArH);7.86-7.94 (m,1H, ArH).

[0205]¹³C-NMR (50 MHz, CDCl₃): 41.8, 41.9 (CH₂Ar); 68.1 (CH₂O); 71.6(CHN); 75.4 (qC); 116.3 (d, J_(CF)=21.8, ArH); 123.5-130.9 (14 ArH);132.5 (d, J_(CF)=17.6, ArH); 136.3, 136.4 (ArCH₂).

Example A8

[0206] Preparation of

[0207] a) Preparation ofN-(1-carboxymethyl-2-hydroxy)ethyl-ferrocenecarbamide

[0208] 431 mg (2.2 mmol) ofN-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) and350 mg (2.2 mmol) of L-serine methyl ester hydrochloride are added at 0°C. to 510 mg (2.2 mmol) of ferrocenecarboxylic acid in 5 mldichloromethane, 363 mg (2.6 mmol) of 1-hydroxybenzotriazole (HOBT) in 2ml of dimethylformamide (DMF) and 73 mg (0.55 mmol) of CuCl₂. After theaddition of 300 mg (3.0 mmol) of triethylamine, the mixture is stirredat RT for 16 h and then extracted with NH₄Cl solution, NaCl solution andNHCO₃ solution (each 2×10 ml). The aqueous phases are extracted againwith ethyl acetate and dried over MgSO₄. After recrystallisation fromethyl acetate, 618 mg (80%) of reddish-brown solid are obtained.

[0209] b) Preparation ofN-(2-hydroxy-1-methylhydroxy-1-methylphenyl-3-phenyl)propyl-ferrocenecarbamide

[0210] Preparation is carried out analogously to Example A4b usingbenzylmagnesium chloride. Column chromatography (15×3 cm, hexanelethylacetate 2:1) yields 194 mg (45%) of solid.

[0211]¹H-NMR (400 MHz, CDCl₃): 2.65 (s, 1H, OH); 2.68 (d, J=14.1, 1H,CH₂—Ar); 2.96 (d, J=14.1, 1H, CH₂—Ar); 3.01 (d, J=13.8, 1H, CH₂—Ar);3.04 (d, J=14.1, 1H, CH₂—Ar); 3.08 (sbr, 1H, OH); 4.04 (mbr, 2H, CH₂—O);4.10-4.13 (mbr, 1H, CH—N); 4.18 (s, 5H, Cp—H); 4.31 (mbr, 2H, Cp—H);4.42 (mbr, 1H, Cp—H); 4.52 (mbr, 1H, Cp—H); 6.22 (d, J=7.58, 1H, NH);7.24-7.27 (m, 4H, Ar—H); 7.30-7.37 (m, 6H, Ar—H).

[0212]¹³C-NMR (80 MHz, CDCl₃): 42.8 (1C, CH₂—Ar); 43.8 (1C, CH₂—Ar);57.2 (1C, CH₂—O); 63.6 (1C, CH—N); 68.0 (1C, Cp—H); 68.0 (1C, Cp—H);69.7 (5C, Cp-H); 70.5 (1C, Cp—H); 76.1 (1C, Cp—H); 76.4 (1C, Cp—H); 77.2(1C, Cp—C); 77.6 (1C, C—O); 127.0 (1C, Ar—H); 127.0 (1C, Ar—H); 128.6(2C, Ar—H); 130.7 (2C, Ar—H); 130.8 (2C, Ar—H); 134.4 (1C, Ar—C); 136.4(1C, Ar—C); 170.0 (1C, C═N).

[0213] c) Preparation of the Title Compound

[0214] Preparation is carried out analogously to Example A4b usingbenzylmagnesium chloride. Column chromatography (15×3 cm, hexane/ethylacetate 2:1) yields 80 mg (94%) of solid.

[0215]¹H-NMR (400 MHz, CDCl₃): 2.65 (s, 1H, OH); 2.68 (d, J=14.1, 1H,CH₂—Ar); 2.96 (d, J=14.1, 1H, CH₂—Ar); 3.01 (d, J=13.8, 1H, CH₂—Ar);3.04 (d, J=14.1, 1H, CH₂—Ar); 3.08 (sbr, 1H, OH); 4.04 (mbr, 2H, CH₂—O);4.10-4.13 (mbr, 1H, CH—N); 4.18 (s, 5H, Cp—H); 4.31 (mbr, 2H, Cp—H);4.42 (mbr, 1H, Cp—H); 4.52 (mbr, 1H, Cp—H); 6.22 (d, J=7.58, 1H, NH);7.24-7.27 (m, 4H, Ar—H); 7.30-7.37 (m, 6H, Ar—H).

[0216]¹³C-NMR (80 MHz, CDCl₃): 42.8 (1C, CH₂—Ar); 43.8 (1C, CH₂—Ar);57.2 (1C, CH₂—O); 63.6 (1C, CH—N); 68.0 (1C, Cp—H); 68.0 (1C, Cp—H);69.7 (5C, Cp—H); 70.5 (1C, Cp—H); 76.1 (1C, Cp—H); 76.4 (1C, Cp—H); 77.2(1C, Cp—C); 77.6 (1C, C—O); 127.0 (1C, Ar—H); 127.0 (1C, Ar—H); 128.6(2C, Ar—H); 130.7 (2C, Ar—H); 130.8 (2C, Ar—H); 134.4 (1C, Ar—C); 136.4(1C, Ar—C); 170.0 (1C, C═N).

Example A9

[0217] Preparation of

[0218] a) Preparation of4-carboxymethyl-2-(3,5-di-tert-butyl)phenyl-oxazoline (A9a)

[0219] 415 mg (1.6 mmol) of 3,5-di-tert-butyl benzimidate are heated atreflux for 18 h with 250 mg (1.6 mmol) of L-serine methyl esterhydrochloride in 20 ml of dichloroethane. After extraction with NaHCO₃solution and NaCl solution (each 2×5 ml), drying over MgSO₄ is carriedout, followed by column chromatography (15×3 cm, diethyl ether/pentane1:3), yielding 342 mg (68%) of a colourless oil.

[0220]¹H-NMR (400 MHz, CDCl₃): 1.34 (s, 9H, CH₃); 3.81 (s, 3H, OCH₃);4.57 (dd, J=10.6/8.6, 1H, OCH₂); 4.68 (dd, J=7.8/8.6, 1H, OCH₂); 4.95(dd, J=10.6/7.8, 1H, NCH); 7.56 (t, J=1.7 , ArH); 7.81 (d, J=1.7, 2H,ArH).

[0221]¹³C-NMR (125 MHz, CDCl₃): 31.7 (9C, CH₃); 35.3 (2C, qC); 53.0 (1C,OCH₃); 69.1 (1C, CHN); 69.8 (1C, OCH₂); 123.2 (1C, ArH); 126.5 (1C,ArH); 126.6 (1C, ArH); 151.4 (2C, ArC); 167.5 (1C, C═N); 172.2 (1C,C═O).

[0222] b)4-(1-Benzyl-1-hydroxy-2-phenyl)ethyl-2-(3,5-di-tert-butylphenyl)oxazoline(A9b)

[0223] 181 mg (0.57 mmol) of compound A9a are dissolved in 20 ml ofdiethyl ether and cooled to −78° C. After the addition of 14 ml of a 1Mbenzylmagnesium chloride solution, the mixture is heated to RT,extracted with NH₄Cl solution and NaCl solution and dried over MgSO₄.Column chromatography (15×2 cm, pentane/diethyl ether 2:1) yields 231.3g (86%) of a colourless, amorphous solid.

[0224]¹H-NMR (400 MHz, CDCl₃): 1.35 (s, 18H, CH₃); 2.01 (s, 1H, OH);2.69 (d, J=13.9, 1H, CH₂Ar); 2.90 (s, 2H, CH₂Ar); 2.98 (d, J=13.6, 1H,CH₂Ar); 4.19-4.35 (m, 3H, CH₂O, CHN); 7.19-7.33 (m, 10H, BnH); 7.56 (t,J=1.7, 1H, ArH); 7.81 (d, J=1.7, 2H, ArH).

[0225]¹³C-NMR (100 MHz, CDCl₃): 31.8 (6C, CH₃); 35.3 (2C, qC); 42.4,42.9 (CH₂Ar); 68.7 (CH₂O); 72.8 (qC); 76.4 (CHN); 123.0 (2C, BnH);126.1, 126.8, 126.9 (ArH); 127.3 (ArC); 128.5, 131.3 (4C, BnH); 137.2,137.5 (ArCH₂); 151.3 (2C, Ar^(t)Bu); 165.9 (C═N).

Example A10

[0226] Preparation of

[0227] a) Preparation of 4-carboxymethyl ester-2-ferrocenyl-oxazoline(A10a)

[0228] Preparation is carried out analogously to Example A9a. Columnchromatography (15×3 cm, hexane/ethyl acetate 1:1) yields 1.4 g (78% oftheory) of a reddish-brown solid.

[0229]¹H-NMR (300 MHz, CDCl₃): 3.82 (s, 3H, OCH₃); 4.22 (s, 5H, CpH);4.37 (quartet, J=1.9, 2H, CpH); 4.46 (dd, J=10.2/8.7, 1H, CH₂O); 4.59(dd, J=8.5/7.1, 1H, CH₂O); 4.78 (dd, J=10.1/7.1, 1H, CHN); 4.76-4.79 (m,1H, CpH); 4.82-4.85 (m, 1H, CpH).

[0230]¹³C-NMR (100 MHz, CDCl₃): 53.0 (1C, OCH₃); 68.9 (1C, CH₂O); 69.2(1C, CpC); 69.7 (1C, CpH); 69.7 (1C, CpH); 70.1 (5C, CpH); 71.0 (1C,CpH); 71.1 (1C, CpH); 77.6 (1C, CHN); 169.9 (1C, C═N); 172.3 (1C, C═O).

[0231] b) Preparation of2-ferrocenyl-4-(1-hydroxy-1-isopropyl-2-methyl)-oxazoline (A10b)

[0232] Preparation is carried out analogously to Example A9b usingisopropylmagnesium chloride. Column chromatography (15×3 cm,hexane/ethyl acetate 1:1) yields 300 mg (53% of theory) of solid.

[0233]¹H-NMR (400 MHz, CDCl₃): 0.96 (d, J=6.8, 3H, CH₃); 0.97 (d, J=7.1,3H, CH₃); 0.98 (d, J=7.1, 3H, CH₃); 1.11 (d, J=7.1, 3H, CH₃); 1.99(septet, J=6.9, 1H, CH); 2.22 (septet, J=7.0, 1H, CH); 2.28 (s, 1H, OH);4.19 (s, 5H, CpH); 4.27 (dd, J=8.1/9.8, 1H, CH₂O); 4.32 (m, 2H, CpH);4.34 (dd, J=8.1/10.1, 1H, CH₂O); 4.45 (dd, J=9.8/10.1, 1H, CHN);4.69-4.70 (m, 1H, CpH); 4.71-4.73 (m, 1H, CpH).

[0234]¹³C-NMR (100 MHz, CDCl₃): 18.5 (2C, CH₃); 18.7 (1C, CH₃); 32.6(1C, CH); 33.8 (1C, CH); 69.0 (1C, CpH); 69.3 (1C, CH₂O); 69.4 (1C,CpH); 69.8 (5C, CpH); 70.5 (1C, CHN); 70.6 (2C, CpH); 71.0 (1C, CpC);77.6 (1C, qC); 166.4 (1C, C═N).

Example A11

[0235] Preparation of

[0236] Preparation is carried out analogously to Example A9b usingisobutylmagnesium chloride. Column chromatography (15×3 cm, hexane/ethylacetate 3:1) yields 500 mg (78% of theory) of solid.

[0237] H-NMR (400 MHz, CDCl₃): 0.94 (d, J=6.57, 3H, CH₃); 1.00 (d,J=6.3, 3H, CH₃); 1.01 (d, J=6.57, 3H, CH₃); 1.02 (d, J=6.3, 3H, CH₃);1.25 (dd, J=14.4/5.2, 1H, CH₂); 1.45 (dd, J=14.6/6.7, 1H, CH₂); 1.56(dd, J=14.6/7.0, 1H, CH₂); 1.64 (s, 1H, OH); 1.68 (dd, J=14.6/5.2, 1H,CH₂); 1.84 (dsept, J=6.5, 2H, CH); 4.22-4.31 (m, 3H, CH₂—O, CH—N); 4.34(quin, J=1.2, 2H, Cp—H); 4.71-4.72 (m,1H, Cp—H); 4.76-4.77 (m, 1H,Cp—H).

[0238]¹³C-NMR (125 MHz, CDCl₃): 23.7 (1C, CH₃); 24.0 (1C, CH₃); 24.6(2C, CH₃); 24.8 (1C, CH); 24.9 (1C, CH); 43.6 (1C, CH₂); 45.4 (1C, CH₂);68.2 (1C, CH₂—O); 69.0 (2C, Cp—H); 69.5 (5C, Cp—H); 70.1 (1C, Cp—C);70.2 (1C, Cp—H); 70.3 (1C, Cp—H); 73.9 (1C, CH—N); 75.8 (1C, Cq); 167.3(1C, C═N).

Example A12

[0239] Preparation of

[0240] a) Preparation of N-benzoyl-L-threonine methyl ester (A12a)

[0241] 3.00 g (17.7 mmol/1 eq) of L-threonine methyl ester hydrochlorideare suspended in 50 ml of methanol, and 7.4 ml (53 mmol/3 eq) oftriethylamine are added thereto. After 10 minutes, the mixture is cooledto 0° C. and the benzoyl chloride (2.74 g/190.5 mmol/1.1 eq) is added.Stirring is carried out at 0° C. for a further two hours. The solvent isthen removed using a rotary evaporator. The solid that remains behind istaken up with ethyl acetate/H₂O (50/20 ml). The aqueous phase isseparated off and extracted by shaking twice more with ethyl acetate (30ml each time). The combined organic phases are washed with 15 ml each ofH₂O and saturated sodium chloride solution, dried over magnesium sulfateand concentrated. 4.07 g (97% of theory) of a white solid are obtained.

[0242]¹H-NMR (400 MHz, CDCl₃): δ=1.29 (d, ³J_(HH)=6.3 Hz, 3H, CH₃), 2.54(s, 1H, OH), 3.80 (s, 3H, OCH₃), 4.45 (dq, ³J_(HH)=2.6 Hz, ³J_(HH)=6.3Hz, 1H, CH—CH₃), 4.83 (dd, ³J_(HH)=2.6 Hz, ³J_(HH)=8.6 Hz, 1H, NH—CH),6.93 (bd, ³J_(HH)=8.6 Hz, 1H, NH), 7.44 (t, ³J_(HH)=7.3 Hz, 2H, PhH),7.47 (t, ³J_(HH)=7.3 Hz, 1H, PhH), 7.84 (d, ³J_(HH)=7.3 Hz, PhH).

[0243] b) Preparation of (4S,5S)-2-phenyl-4-carboxymethyl-5-methyl-oxazoline (A12b)

[0244] 1.07 g (4.5 mmol/1 eq) of compound 12a are dissolved in 10 ml oftetrahydrofuran; 1.18 g (5.0 mmol/1.1 eq) of Burgess reagent are addedand the mixture is heated at 70-80° C. for 2 h. The mixture is thenallowed to cool and 5 ml of water are added. Extraction by shaking 3times with 30 ml of dichloromethane is then carried out. After dryingover magnesium sulfate and removal of the solvent, 0.890 g (95% oftheory) of the oxazoline is obtained in the form of an oil which is usedwithout further purification.

[0245]¹H-NMR (400 MHz, CDCl₃): δ=1.38 (d, ³J_(HH)=6.3 Hz, 3H, CH₃), 3.78(s, 3H, OCH₃), 4.98 (d, ³J_(HH)=10.2 Hz, 1H, C═N—CH), 5.07 (dq,³J_(HH)=6.3 Hz, ³J_(HH)=10.2 Hz, 1H, CH—CH₃), 7.42 (t, ³J_(HH)=7.3 Hz,2H, PhH), 7.48 (t, ³J_(HH)=7.3 Hz, 1H, PhH), 7.98 (d, ³J_(HH)=7.3 Hz,2Hz, 2H, PhH).

[0246] c) Preparation of A12

[0247] 500 mg (2.28 mmol/1 eq) of compound A12b are dissolved in 10 mlof absolute diethyl ether and cooled to −78° C. 6.8 ml (6.8 mmol/3 eq)of a benzylmagnesium chloride solution (1M in hexane) are then slowlyadded dropwise thereto. During 12 hours' subsequent stirring, thereaction mixture assumes room temperature, a white solid beingprecipitated. The supernatant solution is yellow. It is poured into acold ammonium chloride solution. After separation of the phases,extraction is carried out twice more with diethyl ether. The combinedorganic phases are washed with sodium hydrogen carbonate solution andsodium chloride solution and dried over magnesium sulfate. The solventis removed in vacuo. After column chromatography (pentane/ether: 7/1),690 mg (1.86 mmol/82%) of compound A12 are obtained in the form of awhite microcrystalline solid.

[0248]¹H-NMR (400 MHz, CDCl₃): δ=1.73 (d, ³J_(HH)=6.8 Hz, 3H, CH₃), 2.00(s, 1H, OH), 2.69 (d, ²J_(HH)=13.6 Hz, 1H, Ph—CH ₂), 2.93 (d,²J_(HH)=13.9 Hz, 1H, Ph—CH ₂), 3.11 (d, ²J_(HH)=13.9 Hz, 1H, Ph—CH ₂),3.19 (d, ²J_(HH)=13.6 Hz, 1H, Ph—CH ₂), 4.11 (d, ³J_(HH)=9.6 Hz, 1H,C═N—CH), 4.84 (dq, ³J_(HH)=6.8 Hz, ³J_(HH)=9.6 Hz, 1H, CH—CH₃),7.15-7.37 (m, 10H, BnH), 7.44 (t, ³J_(HH)=7.3 Hz, 2H, PhH), 7.50 (t,³J_(HH)=7.3 Hz, 1H, PhH), 8.05 (d, ³J_(HH)=7.3 Hz, 2h, PhH).

Example A13

[0249] Preparation of

[0250] a) Preparation of N-benzoyl-L-allo-threonine methyl ester (A13a)

[0251] Preparation is carried out analogously to Example A12a usingL-allo-threonine methyl ester. 1.2 g (96% of theory) of a crystallinesolid are obtained.

[0252]¹H-NMR (400 MHz, CDCl₃): δ=1.23 (d, ³J_(HH)=6.3 Hz, 3H, CH₃), 3.53(s, 1H, OH), 3.83 (s, 3H, OCH₃), 4.29 (m, 1H, CH—CH₃), 4.88 (dd,³J_(HH)=3.3 Hz, ³J_(HH)=7.1 Hz, 1H, NH—CH), 7.13 (bd, 1H, NH), 7.44 (t,³J_(HH)=7.3 Hz, 2H, PhH), 7.47 (t, ³J_(HH)=7.3 Hz, 1H, PhH), 7.84 (d,³J_(HH)=7.3 Hz, PhH).

[0253] b) Preparation of (4S,5R)-2-phenyl-4-carboxymethyl-5-methyl-oxazoline (A13b)

[0254] Preparation is carried out analogously to Example A12b. 775 mg(80% of theory) of a colourless oil are obtained.

[0255]¹H-NMR (400 MHz, CDCl₃): δ=1.54 (d, ³J_(HH)=6.3 Hz, 3H, CH₃), 3.81(s, 3H, OCH₃), 4.46 (d, ³J_(HH)=7.6 Hz, 1H, C═N—CH), 4.98 (m, 1H,CH—CH₃), 7.39 (t, ³J_(HH)=7.3 Hz, 2H, PhH), 7.48 (t, ³J_(HH)=7.3 Hz, 1H,PhH), 7.98 (d, ³J_(HH)=7.3 Hz, 2H, PhH).

[0256] c) Preparation of A13

[0257] Preparation is carried out analogously to Example A12c. 650 mg(77% of theory) are obtained in the form of a colourless solid.

[0258]¹H-NMR (400 MHz, CDCl₃): δ=1.28 (d, ³J_(HH)=6.3 Hz, 3H, CH₃), 1.77(s, 1H, OH), 2.65 (d, ²J_(HH)=13.9 Hz, 1H, Ph—CH ₂), 2.77 (d,²J_(HH)=13.9 Hz, 1H, Ph—CH ₂), 2.86 (d, ²J_(HH)=13.6 Hz, 1H, Ph—CH ₂),3.07 (d, ²J_(HH)=13.9 Hz, 1H, Ph—CH ₂), 3.80 (d, ³J_(HH)=5.8 Hz, 1H,C═N—CH), 4.89 (m, 1H, CH—CH₃), 7.17-7.35 (m, 10H, BnH), 7.43 (t,³J_(HH)=7.3 Hz, 2H, PhH), 7.50 (t, ³J_(HH)=7.3 Hz, 1H, PhH), 8.05 (d,³J_(HH)=7.3 Hz, 2H, PhH).

Example A14

[0259] Preparation of

[0260] a) Preparation of (3′,5′-dimethylbenzoyl)-L-threonine methylester (A14a)

[0261] 1.00 g (6.66 mmol/1 eq) of 3,5-dimethylbenzoic acid and 1.13 g(6.66 mmol/1 eq) of L-threonine methyl ester hydrochloride are suspendedin 50 ml dichloromethane. At 0° C., 2.04 ml (14.7 mmol/2.2 eq) oftriethylamine are added dropwise. After 10 minutes' stirring, 2.55 g(13.3 mmol/2 eq) of N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimidehydrochloride (EDC) are added, and after a further 15 min1-hydroxybenzotriazole (HOBt) is added. Stirring is carried out fortwelve hours, the solution assuming room temperature. The organic phaseis washed with 10 ml each of H₂O, hydrochloric acid (2N), and NaHCO₃solution. After drying over magnesium sulfate, the solvent is removed invacuo. 1.70 g (6.41 mmol/96%) of a white solid are obtained, which may,if desired, be recrystallised from absolute diethyl ether.

[0262]¹H-NMR (400 MHz, CDCl₃): δ=1.28 (d, ³J_(HH)=6.3 Hz, 3H, CH₃), 2.35(s, 6H, CH₃), 2.42 (s, 1H, OH), 3.79 (s, 3H, OCH₃), 4.45 (m, 1H,CH—CH₃), 4.82 (dd, ³J_(HH)=2.5 Hz, ³J_(HH)=8.7 Hz, 1H, NH—CH), 7.13 (bd,³J_(HH)=8.7 Hz, 1H, NH), 7.14 (s, 1H, PhH), 7.44 (s, 2H, PhH).

[0263] b) Preparation of (4S,5S)-2-(3′,5′-dimethylphenyl)-4-carboxymethyl-5-methyl-oxazoline (A14b)

[0264] Preparation is carried out analogously to Example A12b. 870 mg(78% of theory) of a colourless oil are obtained.

[0265]¹H-NMR (400 MHz, CDCl₃): δ=1.38 (d, ³J_(HH)=6.3 Hz, 3H, CH₃), 2.34(s, 6H, CH₃), 3.78 (s, 3H, OCH₃), 4.96 (d, ³J_(HH)=10.4 Hz, 1H, C═N—CH),5.05 (m, 1H, CH—CH₃), 7.12 (s, 1H, PhH), 7.61 (s, 2H, PhH).

[0266] c) Preparation of compound A14

[0267] Preparation is carried out analogously to Example A12b. 621 mg(69% of theory) of a colourless solid are obtained.

[0268]¹H-NMR (400 MHz, CDCl₃): δ=1.72 (d, ³J_(HH)=6.3 Hz, 3H, CH₃), 2.00(s, 1H, OH), 2.38 (s, 6H, CH₃), 2.70 (d, ²J_(HH)=13.6 Hz, 1H, Ph—CH ₂),2.92 (d, ²J_(HH)=13.9 Hz, 1H, Ph—CH ₂), 3.11 (d, ²J_(HH)=13.9 Hz, 1H,Ph—CH ₂), 3.19 (d, ²J_(HH)=13.6 Hz, 1H, Ph—CH ₂), 4.10 (d, ³J_(HH)=9.3Hz, 1H, C═N—CH), 4.82 (dq, ³J_(HH)=6.3 Hz, ³J_(HH)=9.3 Hz, 1H, CH—CH₃),7.14 (s, 1H, PhH), 7.19-7.35 (m, 10H, BnH), 7.64 (s, 2H, PhH).

Example A15

[0269] Preparation of

[0270] a) Preparation of (3′,5′-di-tert-butyl)benzoyl-L-threonine methylester (A15a)

[0271] Preparation is carried out analogously to Example A14a. 1.80 g(97% of theory) of a colourless solid are obtained.

[0272]¹H-NMR (400 MHz, CDCl₃): δ=1.30 (d, ³J_(HH)=6.3 Hz, 3H, CH₃), 1.34(s, 18H, CCH₃), 2.39 (s, 1H, OH), 3.80 (s, 3H, OCH₃), 4.45 (m, 1H,CH—CH₃), 4.83 (dd, ³J_(HH)=2.5 Hz, ³J_(HH)=8.6 Hz, 1H, NH—CH), 6.90 (bd,³J_(HH)=8.6 Hz, 1H, NH), 7.60 (s, 1H, PhH), 7.65 (s, 2H, PhH).

[0273] b) Preparation of (4S,5S)-2-(3′,5′-di-tert-butyl)phenyl-4-carboxymethyl-5-methyl-oxazoline(A15b)

[0274] Preparation is carried out analogously to Example A12b. 1.17 g(71% of theory) of a colourless oil are obtained.

[0275]¹H-NMR (400 MHz, CDCl₃): δ=1.35 (s, 18H, CCH₃), 1.40 (d,³J_(HH)=6.3 Hz, 3H, CH₃), 3.78 (s, 3H, OCH₃), 4.98 (d, ³J_(HH)=10.1 Hz,1H, C═N—CH), 5.05 (m, 1H, CH—CH₃), 7.57 (s, 1H, PhH), 7.82 (s, 2H, PhH).

[0276] c) Preparation of compound A15

[0277] Preparation is carried out analogously to Example A12b. 1.07 mg(78% of theory) of a colourless solid are obtained.

[0278]¹H-NMR (400 MHz, CDCl₃): δ=1.38 (s, 18H, CCH₃), 1.73 (d,³J_(HH)=6.3 Hz, 3H, CH₃), 2.15 (s, 1H, OH), 2.73 (d, ²J_(HH)=13.9 Hz,1H, Ph—CH ₂), 2.97 (d, ²J_(HH)=13.9 Hz, 1H, Ph—CH ₂), 3.10 (d,²J_(HH)=14.2 Hz, 1H, Ph—CH ₂), 3.20 (d, ²J_(HH)=13.6 Hz, 1H, Ph—CH ₂),4.11 (d, ³J_(HH)=9.6 Hz, ¹H, C═N—CH), 4.82 (dq, ³J_(HH)=6.3 Hz,³J_(HH)=9.6 Hz, 1H, CH—CH₃), 7.24-7.35 (m, 10H, BnH), 7.58 (s, 1H, PhH),7.86 (s, 2H, PhH),

B) PREPARATION OF LIGANDS Example B1

[0279] Preparation of

[0280] Compound A1 is stirred at −78° C. withN,N,N′,N′-tetramethylethylenediamine (TMEDA) (0.3 ml) in 5 ml of diethylether. 0.7 ml of 1.6M n-butyllithium solution is slowly added drop-wisethereto. Stirring is then carried out at RT for 1 h, and then 219 mg(0.99 mmol) of chlorodiphenylphosphine are added and stirring is carriedout for 16 h. The solvent is removed and the solid is purified directlyby column chromatography (15×2 cm, hexane/ethyl acetate, 15:1). 300 mg(57% of theory) of a colourless, amorphous solid are obtained.

[0281]¹H-NMR (300 MHz, CDCl₃): 0.89 (d, J=6.5, 6H, CH₃); 0.89 (d, J=6.5,3H, CH₃); 0.93 (d, J=6.5, 3H, CH₃); 1.27 (s, 9H, CH₃); 1.75-1.91 (m, 6H,CH+CH₂); 4.07 (dd, J=10.3/8.3, 1H, Ox—H); 4.29 (t, J=8.3, 1H, Ox—H);4.54 (dd, J=10.3/7.9, 1H, Ox—H); 7.05-7.07 (m, 2H, Ar—H); 7.17-7.20 (m,3H, Ar—H); 7.32-7.37 (m, 2H, Ar—H); 7.42-7.47 (m, 3H, Ar—H); 7.6(d,J=1.9, 2H, Ar—H).

[0282]³¹P-NMR (120 MHz, CDCl₃): 89.0 (s, OPAr₂).

Example B2

[0283] Preparation of

[0284] Preparation is carried out analogously to Example B1 usingcompound A2. Column chromatography (15×2 cm, hexane/ethyl acetate 5:1)yields 70 mg (63%) of a solid.

[0285]¹H-NMR (300 MHz, CDCl₃): 0.84-0.97 (m, 12H, CH₃); 1.60-1.95 (m,6H, CH₂, CH); 4.10 (t, 1H, CH₂O); 4.35 (t, 1H, CHN); 4.55 (t, 1H, CH₂O);7.05-7.60 (m, 7H, ArH); 7.82 (d, 2H, ArH).

[0286]¹³C-NMR (75 MHz, CDCl₃): 23.5, 23.8 (CH); 25.0, 25.1, 25.2, 25.2(CH₃); 43.6 (d, J_(CP)=9, CH₂); 45.5 (d, J_(CP)=6, CH₂); 68.8 (CH₂O);73.6 (d, J_(CP)=3, CHN); 84.9 (d, J_(CP)6, qC); 126.7-130.6 (aromaticC); 140.4 (ArP); 143.9 (d, J_(CP)=26, ArP); 163.7 (C═N).

[0287]³¹P-NMR (120 MHz, CDCl₃): 89.1 (OPAr₂).

Example B3

[0288] Preparation of

[0289] Preparation is carried out analogously to Example B1 usingcompound A3. Column chromatography (15×2 cm, hexane/ethyl acetate 10:1)yields 105 mg (52%) of a solid.

[0290]¹H-NMR (300 MHz, CDCl₃): 0.88-0.95 (m, 9H, CH₃); 0.96 (d, J=6, 3H,CH₃); 1.65-2.01 (m, 6H, CH₂, CH); 4.12 (dd, J=10.1/8.8, 1H, CH₂O); 4.32(t, J=8.4, 1H, CHN); 4.72 (dd, J=10.1/8.3, 1 H, CH₂O); 7.00-7.17 (m, 4H,ArH); 7.29-7.46 (m, 6H, ArH); 7.79 (d, J=7.7, 2H, NaphH); 7.82 (d,J=7.9, 2H, NaphH); 7.87 (d, J=7.4, 2H, NaphH); 9.25 (d, J=8.2, 1H,NaphH).

[0291]³¹P-NMR (120 MHz, CDCl₃): 89.2 (OPAr₂).

Example B4

[0292] Preparation of

[0293] Preparation is carried out analogously to Example B1 usingcompound A4. After column chromatography (15×2 cm, pentane/diethyl ether10:1), 450 mg (26% of theory) of a yellowish solid are obtained.

[0294]¹H-NMR (400 MHz, CDCl₃): 1.22 (s, 9H, CH₃); 3.01-3.08 (m, 2H,CH₂Ar); 3.18 (dd, J=14.1/1.5, 1H, CH₂Ar); 3.41-3.48 (m, 2H, CH₂Ar,CH₂O); 3.70 (dd, J=8.8/7.8, 1H, CHN); 4.16-4.18 (m, 1H, CH₂O); 7.03-7.15(m, 5H, ArH); 7.20-7.30 (m, 10H, ArH); 7.44-7.51 (m, 5H, ArH).

[0295]³¹P-NMR (160 MHz, CDCl₃): 84.2 (OPAr₂).

Example B5

[0296] Preparation of

[0297] Preparation is carried out analogously to Example B1 usingcompound A5. Column chromatography (15×2 cm, pentaneldiethyl ether 10:1)yields 134 mg (34%) of a solid.

[0298]¹H-NMR (400 MHz, CDCl₃): 0.95 (d, J=7.1, 3H, CH₃); 1.07 (d, J=6.8,3H, CH₃); 1.11, 1.19 (d, J=7.1, 3H, CH₃); 2.48 (dquintet, J=7.1/1.0, 1H,CH); 2.96 (dquintet, J=7.1/3.7, 1H, CH); 4.35 (dd, J=10.6/8.3, CH₂O);4.44 (dd, J=9.3/8.3, CH₂O); 4.77 (t, J=9.9, CHN); 7.04-7.16 (m, 4H,ArH); 7.19-7.28 (m, 4H, ArH); 7.34-7.50 (m, 5H, ArH); 7.80-7.83 (m, 2H,ArH).

[0299]¹³C-NMR (100 MHz, CDCl₃): 17.7, 18.7, 19.8, 20.4 (CH₃); 33.7, 35.8(CH); 69.6 (CH₂O); 70.9 (CHN); 88.0 (qC); 127-131 (aromatic C).

Example B6

[0300] Preparation of

[0301] Preparation is carried out analogously to Example B1 usingcompound A5.

Example B7

[0302] Preparation of

[0303] Preparation is carried out analogously to Example B1 usingcompound A7. Column chromatography (15×2 cm, pentane/diethyl ether 10:1)yields 95 mg (27%) of a solid.

[0304]¹H-NMR (200 MHz, CD₂Cl₂): 3.19 (d, J=14.1, 1H, CH₂); 3.28 (ddd,J=14.1/2.3/1.2, 2H CH₂); 3.69-3.90 (m, 2H, CH₂, CHN); 4.47 (ddd,J=12.1/7.9/1.7, 2H, CH₂O); 7.13-7.65 (m, 23H, ArH); 7.93-8.00 (m, 2H,ArH).

[0305]¹³C-NMR (50 MHz, CD₂Cl₂): 42.9, 43.0, 43.5, 43.8 (CH₂); 68.6(CH₂O); 72.0 (d, J_(CP)=2, qC); 85.6 (d, J_(CP)=8, CHN); 116-133 (arom,C); 137.6 (d, J_(CP)=40, ArP); 144.1 (d, J_(CP)=5, ArC); 144.4 (d, J=8,ArC); 161.3 (C═N); 161.7 (J_(CF)=258, ArF).

[0306]³¹P-NMR (80 MHz, CDCl₃): 83.3.

Example B8

[0307] Preparation of

[0308] Preparation is carried out analogously to Example B1 usingcompound A8. Column chromatography (15×2 cm, pentane/diethyl ether 10:1)yields 97 mg (40%) of a solid.

[0309]¹H-NMR (500 MHz, CD₂Cl₂): 3.10 (d, J=14.0, 1H, CH₂Ar); 3.11 (d,J=13.1, 1H, CH₂Ar); 3.15 (d, J=14.0, 1H, CH₂Ar); 3.38 (d, J=13.1, 1H,CH₂Ar); 3.68 (dd, J=9.9/9.0, 1H, CH₂—O); 3.83 (overlapping dd, J=8.2,1H, CH₂—O); 4.15 (s, 5H, Cp—H); 4.29 (dd, J=9.9/8.4, 1H, CHN); 4.33 (dt,J=2.4/1.3, 1H, Cp—H); 4.36 (dt, J=2.4/1.3, 1H, Cp—H); 4.64 (overlappingtd, J=2.4/1.2, 1H, Cp—H); 4.77 (overlapping td, J=2.4/1.2, 1H, Cp—H);7.08-7.30 (m, 14H, ArH); 7.39-7.48 (m, 6H, ArH).

[0310]¹³C-NMR (125 MHz, CD₂Cl₂): 42.8 (1C, CH₂Ar); 42.9 (1C, CH₂Ar);68.3 (d, J=3.1, 1C, CH₂O); 69.4 (1C, CpH); 69.4 (1C, CpH); 69.8 (5C,CpH); 70.3 (1C, CpH); 70.5 (1C, CpH); 71.4 (1C, CpC); 71.9 (d, J=4.0,1C, CHN); 84.8 (d, J=7.2, 1C, Cq); 126.8 (2C, BnH); 128.3 (2C, BnH);128.3 (2C, BnH); 128.3 (d, J_(C-P)=5, 2C, ArH); 128.4 (d, J_(C-P)=6, 2C,ArH); 128.9 (1C, ArH); 129.1 (1C, ArH); 130.1 (d, J_(C-P)=23, 2C, ArH);130.3 d, J_(C-P)22, 2C, ArH); 131.7, 131.7 (4C, BnH); 137.2, 137.7 (1C,BnC); 144.3 (d, J=16, 1C, ArC); 144.4 (d, J=18, 1C, ArC); 166.4 (1C,C═N).

[0311]³¹P-NMR (160 MHz, CDCl₃): 85.92 (s, OPAr₂).

Example B9

[0312] Preparation of

[0313] Preparation is carried out analogously to Example B1 usingcompound A9. Column chromatography (15×1 cm, pentane/diethyl ether 20:1)yields 77 mg (78%) of a colourless solid.

[0314]¹H-NMR (400 MHz, CD₂Cl₂): 1.37 (s, 18H, H₃CC); 3.12-3.22 (m, 3H,CH₂Ar); 3.62 (d, J=12.9, 1H, ArH); 3.76 (dd, J=10.2/9.0, 1H CH₂O); 3.85(overlapping m, 1H, CHN); 4.48 (ddd, J=10.2/7.9/1.1, 1H, CH₂O);7.04-7.21 (m, 8H, ArH); 7.25-7.30 (m, 6H, ArH); 7.32-7.39 (m, 2H, ArH);7.47-7.51 (m, 2H, ArH); 7.54-7.55 (m; 2H, ArH); 7.60 (t, J=1.8, 1H,ArH); 7.78 (d, J=1.8, 2H, ArH).

[0315]¹³C-NMR (100 MHz, CD₂Cl₂): 31.5 (9C, CH₃); 35.1 (2C, qC); 42.3(1C, CH₂Ar); 43.2 (1C, CH₂Ar); 68.6 (1C, CH₂O); 72.1 (1C, CHN); 85.3(1C, qC); 122.9, 125.8, 126.8, 126.8, 127.7, 128.3, 128.4, 128.4, 129.1,130.0, 130.1, 130.2, 130.4, 131.7 (24C, ArH, ArC).

[0316]³¹P-NMR (160 MHz, CD₂Cl₂): 85.1.

Example B10

[0317] Preparation of

[0318] Preparation is carried out analogously to Example B1 usingcompound A10. Column chromatography (15×1 cm, pentane/diethyl ether10:1) yields 109 mg (46%) of a solid.

[0319]¹H-NMR (CD₂Cl₂, 400 MHz): 0.95 (d, J=6.8, 3H, CH₃); 1.05 (d,J=7.1, 3H, CH₃); 1.12 9d, J=7.1, 3H, CH₃); 1.15 (d, J=7.1, 3H, CH₃);2.56 (dheptet, J=1.5/7.1, 1H, CH); 2.73 (dheptet, J=2.0/7.1, 1H, CH);4.18 (s, 5H, CpH); 4.27-4.38 (m, 4H, 2*CpH, CH₂O); 4.48 (quintet, J=1.2,1H, CpH); 4.65-4.70 (m, 1H, CHN); 4.71 (quintet, J=1.2, 1H, CpH);7.23-7.33(m, 6H, ArH); 7.48-7.54 (m, 4H, ArH).

[0320]¹³C-NMR (CD₂Cl₂, 100 MHz): 18.7 (d, J_(CP)=1.5, 1C, CH₃); 19.2 (d,J_(CP)=2, 1C, CH₃); 19.3 (d, J_(CP)=1.5, 1C, CH₃); 19.4 (d, J_(CP)=1.5,1C, CH₃); 33.7 (d, J_(CP)=7, 1C, CH); 34.1 (d, J_(CP)=6, 1C, CH); 69.1(1C, CpH); 69.3 (d, J_(CP)=3, 1C, CH₂O); 69.4 (1C, CpH); 69.7 (5C, CpH);70.1 (1C, CpH); 70.4 (1C, CpH); 71.2 (d, J_(CP)=4, 1C, NCH); 87.9 (d,J_(CP)=5, 1C, Cq); 128.4 (d, J_(CP)=4, 1C, ArH); 128.5 (d, J_(CP)=3, 1C,ArH); 128.8 (1C, ArH); 129.2 (1C, ArH); 129.6 (d, J_(CP)=24, 2C, ArH);130.7 (d, J_(CP)=25, 2C, ArH); 144.7 (d, J_(CP)=19, 1C, ArP); 145.5 (d,J_(CP)=18, 1C, ArP); 165.9 (1C, C═N).

[0321]³¹P-NMR (160 MHz, CD₂Cl₂): 85.2 (d, OPAr₂).

Example B11

[0322] Preparation of

[0323] Preparation is carried out analogously to Example B1 usingcompound A11. Column chromatography (15×1 cm, pentane/diethyl ether 6:1)yields 74.6 mg (50%) of a solid.

[0324]¹H-NMR (400 MHz, CD₂Cl₂): 0.97 (d, J=6.5, 3H, CH₃); 0.98 (d,J=6.3, 3H, CH₃); 0.99 (d,J=5.3, 3H, CH₃); 1.05 (d, J=6.5, 3H, CH₃);1.67-1.79 (m, 2H, CH₂); 1.93-2.03 (m, 2H, CH₂); 4.08 (dd, J=8.8/10.1,1H, CH₂O); 4.18 (s, 5H, CpH); 4.24 (dd, J=8.4/7.9, 1H, CH₂O); 4.31-4.33(m, 2H, CpH); 4.53 (dd, J=10.2/7.9, 1H, CHN); 4.61-4.62 (m, 1H, CpH);4.65-4.66 (m, 1H, CpH); 7.25-7.35 (m, 6H, ArH); 7.49-7.59 (m, 4H, ArH).

[0325]¹³C-NMR (100 MHz, CD₂Cl₂): 23.7 (1C, CH); 23.9 (1C, CH); 25.1 (1C,CH₃); 25.3 (1C, CH₃); 25.4 (1C, CH₃); 25.5 (1C, CH₃); 43.9 (d, J_(CP)=6,1C, CH₂); 45.0 (d, J_(CP)=8, 1C, CH₂); 69.0 (d, J_(CP)=3, 1C, CH₂O);69.2 (1C, CpH); 69.4 (1C, CpH); 69.7 (1C, CpH); 69.7 (1C, CpH); 69.7(5C, CpH); 70.3 (1C, CpH); 71.4 (1C, CpH); 73.7 (d, J_(CP)=5, 1C, CHN);85.1 (d, J_(CP)=7, 1C, qC); 128.4 (d, J_(CP)=7, 4C, ArH); 128.9 (1C,ArH); 129.0 (1C, ArH); 130.1 (d, J_(CP)=24, 2C, ArH); 130.5 (d,J_(CP)=24, 2C, ArH).

[0326]³¹P-NMR (160 MHz, CD₂Cl₂): 85.5 (d, OPAr₂).

Example B12

[0327] Preparation of

[0328] Preparation is carried out analogously to Example B1 usingcompound A12. Column chromatography (ethyl acetate/hexane/triethylamine:1/15/0.001) yields 310 mg (56% of theory) of a microcrystalline solid.

[0329]¹H-NMR (400 MHz, CDCl₃): δ=1.24 (d, ³J_(HH)=6.6 Hz, 3H, CH₃), 3.11(d, ²J_(HH)=14.4 Hz, 1H, Ph—CH ₂), 3.33 (d, ²J_(HH)=13.4 Hz, 2H, Ph—CH₂), 3.72 (d, ²J_(HH)=12.9 Hz, 1H, Ph—CH ₂), 4.34 (d, ³J_(HH)=9.6 Hz, 1H,C═N—CH), 4.73 (m, 1H, CHCH₃), 7.05-7.50 (m, 23H, BnH, PhH, PPhH), 8.01(d, ³J_(HH)=7.3 Hz, 2H, PhH).

[0330]³¹P{¹H}-NMR (161.9 MHz, CDCl₃): δ=88.7.

Example B13

[0331] Preparation of

[0332] Preparation is carried out analogously to Example B1 usingcompound A13. Column chromatography. (ethylacetate/hexane/triethylamine: 1/15/0.001) yields 270 mg (41% of theory)of a microcrystalline solid.

[0333]¹H-NMR (400 MHz, CDCl₃): δ=1.01 (d, ³J_(HH)=6.0 Hz, 3H, CH₃), 3.08(d, ²J_(HH)=14.2 Hz, 1H, Ph—CH ₂), 3.14 (dd, ⁴J_(HP)=2.8 Hz,²J_(HH)=12.9 Hz, 1H, Ph—CH ₂), 3.18 (d, ²J_(HH)=14.2 Hz, 1H, Ph—CH),3.51 (d, ²J_(HH)=12.9 Hz, 1H, Ph—CH ₂), 4.00 (d, ³J_(HH)=4.8 Hz, 1H,C═N—CH), 4.69 (m, 1H, CH—CH₃), 7.02-7.55 (m, 23H, BnH, PhH, PPhH), 7.95(d, ³J_(HH)=7.3 Hz, 2H, PhH).

[0334]³¹P{¹H}-NMR (161.9 MHz, CDCl₃): δ=85.3.

Example B14

[0335] Preparation of

[0336] Preparation is carried out analogously to Example B1 usingcompound A14. Column chromatography (ethyl ether/pentane: 1/25) yields404 mg (53% of theory) of a microcrystalline solid.

[0337]¹H-NMR (400 MHz, CDCl₃): δ=1.26 (d, ³J_(HH)=6.6 Hz, 3H, CH₃), 2.34(s, 6H, PhCH₃), 3.10 (d, ²J_(HH)=14.1 Hz, 1H, Ph—CH ₂), 3.33 (bd, 2H,Ph—CH ₂), 3.67 (d, ²J_(HH)=12.9 Hz, 1H, Ph—CH ₂), 4.35 (d, ³J_(HH)=9.3Hz, 1H, C═N—CH), 4.71 (m, 1H, CH—CH₃), 7.10-7.50 (m, 21H, BnH, PhH,PPhH), 7.61 (s, 2H, PhH).

[0338]³¹P{¹H}-NMR (161.9 MHz, CDCl₃): δ=88.6.

Example B15

[0339] Preparation of

[0340] Preparation is carried out analogously to Example B1 usingcompound A15. Column chromatography (ethyl ether/pentane: 1/25) yields318 mg (51% of theory) of a microcrystalline solid.

[0341]¹H-NMR (400 MHz, CDCl₃): δ=1.33 (d, ³J_(HH)=6.3 Hz, 3H, CH₃), 1.39(s, 18H, C(CH₃)₃), 3.11 (d, ²J_(HH)=14.2 Hz, 1H, Ph—CH ₂), 3.31 (d,³J_(HH)=13.4, 1H, Ph—CH ₂), 3.40 (d, ²J_(HH)=14.6, 1H, Ph—CH₂) 3.63 (d,²J_(HH)=12.9 Hz, 1H, Ph—CH ₂), 4.33 (d, ³J_(HH)=9.1 Hz, 1H, C═N—CH),4.71 (m, 1H, CH—CH₃), 7.05-7.51 (m, 20H, BnH, PPhH), 7.57 (s, 1H, PhH),7.86 (s, 2H, PhH).

[0342]³¹P{¹H}-NMR (161.9 MHz, CDCl₃): δ=88.1.

Example B16

[0343] Preparation of

[0344] Preparation is carried out analogously to Example B1 usingcompound A12 and chloro-di-ortho-tolyl-phosphine. Column chromatography(ethyl acetate/hexane/triethylamine: 1/15/0.001) yields 160 mg (51% oftheory) of a microcrystalline solid.

[0345]¹H-NMR (400 MHz, CDCl₃): δ=1.00 (d, ³J_(HH)=6.6 Hz, 3H, CH₃), 2.20(s, 3H, PhCH₃), 2.47 (s, 3H, PhCH₃), 3.16 (d, ²J_(HH)=14.2 Hz, 1H, Ph—CH₂), 3.24 (d, ²J_(HH)=14.2 Hz, 1H, Ph—CH ₂), 3.35 (dd, ⁴J_(PH)=2.5 Hz,³J_(HH)=13.1 Hz, 1H, Ph—CH ₂), 3.79 (d, ²J_(HH)=12.9 Hz, 1H, Ph—CH ₂),4.41 (d, ³J_(HH)=9.1 Hz, 1H, C═N—CH), 4.62 (m, 1H, CH—CH₃), 6.95-7.28(m, 16H, ArH), 7.41-7.52 (m, 5H, ArH), 7.71 (m, 1H, ArH), 8.03 (m, 2H,ArH).

[0346]³¹P{¹H}-NMR (161.9 MHz, CDCl₃): δ=70.7.

Example B17

[0347] Preparation of

[0348] Preparation is carried out analogously to Example B1 usingcompound A6 and chlorodicyclohexylphosphine. Column chromatography (15×2cm, hexane/ethyl acetate 10:1) yields 512 mg (52%) of a solid.

[0349]¹H-NMR (400 MHz, CDCl₃): δ=0.92-2.05 (complex m, 22H, CH and CH ₂cyclohexyl), 2.87 (d, ²J_(HH)=13.9 Hz, 1H, Ph—CH ₂), 2.95 (d,²J_(HH)=12.6 Hz, 1H, Ph—CH ₂), 3.04 (d, ²J_(HH)=13.9 Hz, 1H, Ph—CH ₂),3.74-3.88 (m, 2H, O—CH ₂ and Ph—CH ₂), 4.00 (d, ³J_(HH)=6.8 Hz, 1H,C═N—CH), 4.31 (m, 1H, O—CH ₂), 7.18-7.34 (m, 8H, ArH), 7.39-7.52 (m, 3H,ArH), 7.63 (m, 2H, ArH), 7.94 (m, 2H, ArH).

[0350]³¹P{¹H}-NMR (161.9 MHz, CDCl₃): δ=122.3.

Example B18

[0351] Preparation of

[0352] Preparation is carried out analogously to Example B1 usingcompound A9 (starting from D-serine methyl ester) andchlorodicyclohexylphosphine. Column chromatography (15×2 cm,hexane/ethyl acetate 10:1) yields 730 mg (50%) of a solid.

[0353]¹H-NMR (400 MHz, CDCl₃): δ=0.71-2.20 (complex m, 40H, CH and CH ₂cyclohexyl, tert-butyl CH ₃), 2.71-3.02 (m, 4H, PhCH ₂), 4.00 (d,J_(HH)=11.9 Hz, 1H, O—CH ₂), 4.25 (m, 1H, C═N—CH), 4.73 (d, J_(HH)=8.1Hz, 1H, O—CH ₂), 6.91-7.42 (m, 10H, ArH), 7.42-7.64 (m, 2H, ArH), 7.81(sb, 1H, ArH)

[0354]³¹P{¹H}-NMR (161.9 MHz, CDCl₃): δ=121.7.

C) PREPARATION OF CATALYSTS

[0355] The catalysts prepared according to Examples C1-C18 correspond toformula

[0356] (COD) Ir L)⁺ tetrakis(3,5-bistrifluoromethylphenyl) borate,

[0357] wherein L is a ligand according to Examples B1 to B18 and COD iscyclooctadiene. Sodium tetrakis(3,5-bistrifluoromethylphenyl) borate isabbreviated to NaBARF hereinbelow.

Example C1

[0358] Ir Catalyst C1 with Ligand B1

[0359] 57 mg (0.097 mmol) of compound B1 are dissolved in 5 ml ofdichloromethane. After the addition of 34.7 mg (0.051 mmol) of[CODIrCl]₂, the mixture is heated at reflux and allowed to react until asolution has been formed and the reaction is complete. Then, withvigorous stirring, 91 mg (0.1 mmol) of NaBARF and 3 ml of water areadded. After column chromatography (15×2 cm, pentaneldiethyl ether10:1), 450 mg (26% of theory) of a yellowish solid are obtained.

[0360]¹H-NMR (400 MHz, CDCl₃): −0.16 (d, J=6.6, 3H, CH₃); 0.50 (d,J=6.3, 3H, CH₃); 0.98-1.13 (m, 2H, CH₂); 0.99 (d, J=6.6, 3H, CH₃); 1.08(d, J=6.8, 3H, CH₃); 1.25-1.50 (m, 4H, CH, CH₂, CH₂COD); 1.60-1.80 (m,2H, CH₂COD); 1.90 (dd, J=15.4/3.9, 1H, CH₂); 2.15-2.20 (m, 2H, CH, CH₂,CH₂COD); 2.25-2.40 (m, 2H, CH₂COD, CHCOD); 2.45-2.52 (m, 2H, CH₂COD);3.25 (m, 1H, CHCOD); 4.07 (m, 1H, CHCOD); 4.58 (dd, J=10.1/3.9, 1H,CH₂O); 4.78 (overlapping dd, J=10.1/9.8, 1H, CHN); 4.79-4.87 (mbr, 1H,CHCOD); 5.33 (dd, J=9.8/3.9, 1H, CH₂O); 7.18-7.24 (m, 2H, ArH);7.40-7.50 (m, 3H, ArH); 7.51 (sbr, 4H, BARF-H); 7.58-7.64 (m, 2H, ArH);7.66-7.72 (m, 1H, ArH); 7.78 (d, J=1.8, 2H, PhH); 7.83 (t, J=1.8, PhH);8.15-8.23 (m, 2H, ArH).

[0361]¹³C-NMR (100 MHz, CDCl₃): 22.7 (CH₃); 23.3 (2C, CH₃); 24.6(CH₂COD); 25.0 (CH); 25.1 (CH); 26.1 (CH₃); 26.3 (CH₂COD); 31.6 (6C,CH₃); 35.6 (qC); 36.5 (CH₂); 46.5 (CH₂); 62.0 (CHCOD); 68.5 (CHCOD);70.1 (CH₂O); 72.2 (d, J_(CP)=5, CHN); 77.6 (CHCOD); 89.9 (d, J_(CP)=6,qC); 103.7 (CHCOD); 117.8 (m, 4C, BARF); 123-134 (aromatic C); 135.2 (m,8C, BARF); 161 (q, J_(CB)=49, ArB); 174.9 (C═N).

[0362]³¹P-NMR (160 MHz, CDCl₃): 92.2.

Example C2

[0363] Ir catalyst C2 with Ligand B2

[0364] Preparation is carried out analogously to Example C1. Yield: 100mg (39% of theory) of an orange solid.

[0365]¹H-NMR (400 MHz, CDCl₃): −0.17 (d, J=6.82, 3H, CH₃); 0.76 (d,J=6.32, 3H, CH₃); 0.98-1.05 (m, 1H, CH₂); 0.99 (d, J=6.57, 3H, CH₃);1.08-1.15 (m, 1H, CH₂); 1.12 (d, J=6.57, 3H, CH₃); 1.20-1.30 (m, 1H,CH₂COD); 1.40-1.60 (m, 3H, CH, CH₂, CH₂COD); 1.70-1.83 (m, 2H, CH₂COD);1.95 (dd, J=15.4/3.8, 1H, CH₂); 2.10-2.20 (m, 2H, CH, CH₂COD); 2.28-2.60(m, 4H, CHCOD, CH₂COD); 3.84 (sbr, 1H, CHCOD); 3.94 (mbr, 1H, CHCOD);4.59 (dd, J=10.1/3.3, 1H, CH₂O); 4.71 (overlapping dd, J=10.1/9.3, 1H,CHN); 5.04 (mbr, 1H, CHCOD); 5.22 (dd, J=9.3/3.3, 1H, CH₂O); 7.20-7.25(m, 2H, ArH); 7.42-7.55 (m, 6H, ArH, Biphen); 7.59 (sbr, 4H, BARF-H);7.60-7.73 (m, 6H, ArH, Biphen); 7.71 (sbr, 8H, BARF-H); 7.85 (d, J=8.6,2H, Biphen); 8.03-8.08 (m, 2H, ArH); 8.41 (d, J=8.4, 2H, Biphen).

[0366]¹³C-NMR (100 MHz, CDCl₃): 22.7 (CH₃); 23.5 (2C, CH₃); 24.8(CH₂COD); 25.0 (CH); 25.3 (CH₃); 26.0 (CH₂COD); 29.3 (CH); 32.2(CH₂COD); 36.7 (d, CH₂); 41.6 (CH₂COD); 46.5 (d, J_(CP)=7, CH₂); 65.0(CHCOD); 69.5 (CHCOD); 70.4 (CH₂O); 71.6 (CHCOD); 77.6 (qC); 90.2 (d,J_(CP)=7, CHN); 103.5 (d, J_(CP)=11, CHCOD); 117.8 (m, 4C, BARF);120.8-136 (aromatic C); 135.2 (m, 8C, BARF); 138.8 (ArP); 149.1 (ArP);162.8 (q, J_(CB)=49, ArB); 172.4 (C═N).

[0367]³¹P-NMR (160 MHz, CDCl₃): 93.8.

Example C3

[0368] Ir Catalyst C3 with Ligand B3

[0369] Preparation is carried out analogously to Example C1. Yield: 98mg (28% of theory) of an orange solid.

[0370] hu 1H-NMR (400 MHz, CDCl₃): 0.00 (d, J=6.6, 3H, CH₃); 0.82 (d,J=6.3, 3H, CH₃); 1.00 (d, J=6.8, 3H, CH₃); 1.09 (d, J=6.8, 3H, CH₃);1.18-1.43 (m, 4H, CH₂, CH₂COD); 1.49-1.68 (m, 3H, CH₂, CH, CH₂COD);1.71-1.83 (m, 1H, CH₂COD); 1.93-2.06 (m, 2H, CH₂, CH₂COD); 2.10-2.33 (m,4H, CH, CH₂COD); 2.41 (mbr, 1H, CHCOD); 3.30 (mbr, 1H, CHCOD); 3.39(mbr, 1H, CHCOD); 4.72-4.80 (mbr, 1H, CHCOD); 4.74 (dd, J=10.1/4.0, 1H,CH₂O); 5.02 (overlapping dd, J=10.1/9.8, 1H, CHN); 5.27 (dd, J=9.8/4.0,1H, CH₂O); 7.25-7.29 (m, 3H, ArH); 7.42-7.48 (m, 3H, ArH); 7.51 (sbr,4H, BARF-H); 7.62-7.72 (m, 7H, ArH); 7.72 (sbr, 8H, BARF-H); 7.97-8.03(m, 2H, ArH); 8.10-8.18 (m, 2H, ArH); 8.21-8.25 (m, 2H, ArH).

[0371]¹³C-NMR (100 MHz, CDCl₃): 22.8 (CH); 23.4 (CH₃); 24.9 (CH); 25.0(CH₃); 25.1 (CH₃); 26.1 (CH₃); 26.5 (CH₂COD); 29.5 (CH₂COD); 31.1(CH₂COD); 35.5 (CH₂COD); 42.3 (CH₂); 46.6 (d, J=6, CH₂); 63.0 (CHCOD);68.2 (CH₂O); 71.2 (d, J=5, qC); 71.3 (CHCOD); 90.1 (d, J=7, CHN); 97.8(d, J=13, CHCOD); 102.7 (d, J=12, CHCOD); 117.8 (m, 4C, BARF);120.9-137.2 (arom, C); 135.2 (m, 8C, BARF); 162.1 (q, J_(CB)=49, ArB);175.1 (C═N).

[0372]³¹P-NMR (160 MHz, CDCl₃): 92.4.

Example C4

[0373] Ir Catalyst C4 with Ligand B4

[0374] Preparation is carried out analogously to Example C1. Columnchromatography (15×2 cm, dichloromethane) yields 339 mg (78%) of solid.

[0375]¹H-NMR (400 MHz, CD₂Cl₂): 1.32-1.43 (m, 1H, CH₂COD); 1.57 (s, 9H,CH₃); 1.60-1.77 (m, 2H, CH₂COD); 2.07-2.29 (m, 3H, CH₂COD); 2.40-2.46(m, 1H, CH₂COD); 2.49-2.57 (m, 1H, CH₂COD); 2.58 (d, J=15.4, 1H, CH₂Ar);2.77 (dd, J=15.2/5.1, 1H, CH₂Ar); 2.82 (d, J=15.2, 1H, CH₂Ar); 3.15 (d,J=14.6, 1H, CH₂Ar); 3.88 (mbr, 1H, CHCOD); 4.36-4.43 (m, 1H, CHCOD);4.64 (overlapping dd, J=9.6/10.1, 1H, CHN); 4.76 (dd, J=10.4/3.1, 1H,CH₂O); 5.12 (dd, J=9.3/3.1, 1H, CH₂O); 5.06-5.13 (m, 1H, CHCOD); 5.33(m, 1H, CHCOD); 6.97-7.02 (m, 4H, ArH); 7.10-7.13 (m, 2H, ArH);7.22-7.26 (m, 3H, ArH); 7.37-7.42 (m, 2H, ArH); 7.42-7.52 (m, 4H, ArH);7.57 (sbr, 4H, BARF-H); 7.58-7.62 (m, 2H, ArH); 7.66-7.71 (m, 1H, ArH);7.74 (sbr, 8H, BARF-H); 8.00-8.06 (m, 2H, ArH).

[0376]¹³C-NMR (100 MHz, CDCl₃): 25.4 (CH₂COD); 28.2 (CH₂COD); 29.3 (3C,CH₃); 33.7 (CH₂COD); 34.9 (qC); 37.3 (d, J_(CP)=3, CH₂Ar); 39.3(CH₂COD); 44.1 (d, J_(CP)=6, CH₂Ar); 65.9 (CHCOD); 68.8 (CHCOD); 69.8(CH₂O); 73.2 (d, J_(CP)=4.6, CHN); 88.1 (d, J_(CP)=7.6, qC); 91.4 (d,J_(CP)=15.3, CHCOD); 100.9 (d, J_(CP)=10.7, CHCOD); 117.8 (m, 4C,BARF-H); 123.6-135.7 (ArH, ArC, ArP, CF₃); 162.0 (q, J_(CB)=49, ArB);184.7 (C═N).

[0377]³¹P-NMR (160 MHz, CDCl₃): 99.1.

Example C5

[0378] Ir Catalyst C5 with Ligand B5

[0379] Preparation is carried out analogously to Example C1. Columnchromatography (15×1 cm, diethyl ether/dichloromethane 5:1) yields 109mg (47%) of red solid.

[0380]¹H-NMR (400 MHz, CDCl₃): 0.62 (d, J=6.8, 3H, CH₃); 0.91 (d, J=6.8,3H, CH₃); 0.97 (d, J=7.1, 3H, CH₃); 1.17 (d, J=6.6, 3H, CH₃); 1.59-1.69(m, 2H, CH₂—COD); 1.73-1.81 (m, 1H, CH₂—COD); 1.88-1.97 (m, 1H,CH₂—COD); 2.00-2.05 (m, 1H, CH₂—COD); 2.16 - 2.47 (m, 5H, 2 CH(CH₃), 3CH₂—COD); 2.82 (m, 1H, CH—COD); 3.81 (m, 1H, CH—COD); 3.90 (m, 1H,CH—COD); 4.67-4.75 (m, 2H, CH₂O); 4.80 (m, 1H, CH—COD); 5.18 (dd,J=6.0/10.1, CHN); 7.34-7.40 (m, 2H, ArH); 7.51 (sbr, 4H, BarfH);7.44-7.59 (m, 8H, ArH); 7.71 (sbr, 9H, 8 BarfH, ArH); 7.85-7.90 (m, 2H,ArH); 8.21 (d, J=7.3, 2H, ArH).

[0381]¹³C-NMR (100 MHz, CDCl₃): 18.8, 18.8, 18.9, 19.4 (CH₃); 26.9, 30.5(CH₂COD); 31.3, 34.1 (CH(CH₃)); 34.8, 35.5 (CH₂COD); 64.6 (CHCOD); 67.5(CH₂O); 70.4 (CHCOD); 70.9 (d, J_(CP)=6, CHN); 93.3 (d, J_(CP)=8, qC);95.9 (d, J_(CP)=13, CHCOD); 101.7 (d, J_(CP)=12, CHCOD); 117.8 (m, 4C,ArH); 123.5-137.2 (arom, C); 135.1 (br, 8C, ArBarf); 162.1 (q withappearance of t, J_(CB)=49, ArB); 174.1 (C═N).

[0382]³¹P-NMR (160 MHz, CDCl₃): 94.02 (OPAr₂).

Example C6

[0383] Ir Catalyst C6 with Ligand B6

[0384] Title compound B6 is prepared analogously to Example C1.

Example C7

[0385] Ir Catalyst C7 with Ligand B7

[0386] Preparation is carried out analogously to Example C1. Columnchromatography (15×1 cm, dichloromethane) yields 207 mg (57% of theory)of orange solid.

[0387]¹H-NMR (300 MHz, CDCl₃): 1.14-1.30 (m, 2H, CH₂COD); 1.31-1.65 (m,2H, CH₂COD); 1.90-2.35 (m, 5H, CHCOD, CH₂COD; 2.73 (d, J=14.6, 1H, CH₂);2.76 (dd, J=14.7/5.6, 1H, CH₂); 2.94 (d, J=18.1, 1H, CH₂); 2.99 (d,J=17.9, 1H, CH₂); 3.17 (m, 1H, CHCOD); 3.72 (m, 1H, CHCOD); 4.50-4.60(m, 1H, CH₂O); 4.63-4.70 (m, 1H, CHCOD); 4.78-4.88 (m, 2H, CH₂O, CHN);6.67-6.69 (m, 2H, ArH); 6.88-7.15 (m, 7H, ArH); 7.28-7.41 (m, 8H, ArH);7.43 (sbr, 4H, BARF-H); 7.58-7.73 (m, 2H, ArH); 7.64 (sbr, 8H, BARF-H);8.05-8.15 (m, 2H, ArH).

[0388]¹³C-NMR (75 MHz, CDCl₃): 26.5, 29.1, 32.4, 35.6 (CH₂COD); 41.8,44.4 (CH₂); 63.3 (CHCOD); 68.2 (qC); 70.2 (CHCOD); 77.6 (qC); 88.6(CHN); 95.2, 102.2 (CHCOD); 117-135 (aromatic C).

Example C8

[0389] Ir Catalyst C8 with Ligand B8

[0390] Preparation is carried out analogously to Example C1. Columnchromatography (15×2 cm, diethyl ether/dichloromethane 6:1) yields 125mg (98%) of solid.

[0391]¹H-NMR (600 MHz, CDCl₃): 1.31-1.37 (m, 1H, CH₂—COD); 1.48-1.63 (m,2H, CH₂—COD); 1.80 (m, 1H, CH₂—COD); 2.11-2.13 (m, 3H, CH₂—COD, CH—COD);2.30-2.37 (m, 1H, CH₂—COD); 2.42-2.49 (m, 1H, CH₂—COD); 2.68 (dd,J=15.2/5.3, 1H, CH₂Ar); 2.82 (d, J=15.2, 1H, CH₂Ar); 2.96 (d, J=15.2,1H, CH₂Ar); 3.16 (d, J=15.2, 1H, CH₂Ar); 3.66 (sbr, 1H, CH—COD); 4.15(s, 5H, CpH); 4.15-4.19 (m, 1H, CH—COD); 4.67 (t, J=9.5, 1H, CH₂O); 4.73(m, 1H, CpH); 4.74 (m, 1H, CH₂O); 4.76 (quartet, J=1.2, 1H, CpH); 4.85(dd, J=9.7/3.1, 1H, CHN); 4.89 (t, J=1.2, 1H, CpH); 4.95 (quartet,J=3.9, 1H, CH—COD); 5.62 (t, J=1.2, 1H, CpH); 6.82 (d, J=7.1, 2H, ArH);7.01-7.04 (m, 4H, ArH); 7.15-7.21 (m, 3H, ArH); 7.36-7.42 (m, 5H, ArH);7.51 (mbr, 5H, 4 BARF-H, ArH); 7.71 (mbr, 11H, 8 BARF-H, 3 ArH); 8.21(dd, J=6.8/11.8, 2H, ArH).

[0392]³¹P-NMR (160 MHz, CD₂Cl₂): 97.2 (s, OPAr₂).

Example C9

[0393] Ir Catalyst C9 with Ligand B9

[0394] Preparation is carried out analogously to Example C1. Columnchromatography (15×2 cm, diethyl ether/dichloromethane 6:1) yields 125mg (98%) of solid.

[0395]¹H-NMR (400 MHz, CDCl₃): 1.25-1.34 (m, 2H, CH₂cod); 1.44 (s, 18H,H₃CC); 1.60-1.70 (m, 2H, CH₂cod); 2.03-2.21 (m, 3H, CH₂cod, CHcod);2.37-2.51 (m, 2H, CH₂cod); 2.72 (d, J=14.6, 1H, CH₂Ar); 2.89 (dd,J=14.9/5.5, 1H, CH₂Ar); 2.96 (d, J=14.9, 1H, CH₂Ar); 3.01 (d, J=14.6,1H, CH₂Ar); 3.26 (mbr, 1H, CHcod); 4.04-4.11 (m, 1H, CHcod); 4.68 (dd,J=10.1/3.3, 1H, CH₂O); 4.75 (mbr, 1H, CHcod); 4.89 (t, J=10.1, 1H, CHN);5.02 (dd, J=10.1/3.3, 1H, CH₂O); 6.68-6.71 (m, 2H, ArH); 6.91-7.19 (m,7H, ArH); 7.32-7.48 (m, 6H, ArH); 7.50 (s, 4H, BARF-H); 7.66-7.79 (m,11H, BARF-H, ArH); 7.87-7.89 (m, 3H, ArH); 8.25-8.30 (m, 2H, ArH).

Example C10

[0396] Ir Catalyst C10 with Ligand B10

[0397] Preparation is carried out analogously to Example C₁. Columnchromatography (15×2 cm, diethyl ether/dichloromethane 5:1) yields 140mg (83%) of solid.

[0398]¹H-NMR (400 MHz, CDCl₃): 0.77 (d, J=6.8, 3H, CH₃); 0.91 (d, J=7.1,3H, Ch₃); 1.15 (d, J=6.6, 3H, CH₃); 1.28 (d, J=6.6, 3H, CH₃); 1.70-1.84(m, 2H, CH₂cod); 1.96-2.01 (m, 3H, CH₂cod, CH); 2.08-2.21(m, 2H,CH₂cod); 2.36-2.45 (m, 1H, CH); 2.45-2.54 (m, 2H, CH₂cod); 2.97 (m, 1H,CHcod); 3.80 (m, 1H, CHcod); 4.06 (s, 5H, CpH); 4.35 (m, 1H, CHcod);4.48 (dd, J=10.7/9.9, 1H, CH₂O); 4.59 (dd, J=9.7/6.8, 1H, CH₂O); 4.67(m, 1H, CpH); 4.70 (m, 1H, CpH); 4.77 (dd, J=10.7/6.3, 1H, CHN); 4.84(m, 1h, CHcod); 4.93 (m, 1H, CpH); 5.24 (m, 1H, CpH); 7.29-7.34 (m, 2H,ArH); 7.46-7.48 (m, 3H, ArH); 7.52 (s, 4H, ArH BARF); 7.50-7.59 (m, 3H,ArH); 7.71 (s, 8H, ArH BARF); 7.83-7.88 (m, 2H, ArH).

[0399]³¹P-NMR (160 MHz, CDCl₃): 93.47 (OPAr₂).

Example C11

[0400] Ir Catalyst C11 with Ligand B11

[0401] Preparation is carried out analogously to Example C1. Columnchromatography (15×2 cm, diethyl ether/dichloromethane 5:1) yields 195mg (87%) of solid.

[0402]¹H-NMR (400 MHz, CDCl₃): −0.09 (d, J=6.8, 3H, CH₃); 0.92 (d,J=6.3, 3H, CH₃); 0.97 (d, J=6.6, 3H, CH₃); 1.09- 1.18 (m, 1H, CH₂); 1.16(d, J=6.8, 3H, CH₃); 1.38-1.50 (m, 3H, CH₂, CH₂cod); 1.51-1.70 (m, 2H,CH, CH₂cod); 1.70-1.83 (m, 2H, CH₂cod); 1.98 (dd, J=15.4/3.8, 1H, CH₂);2.12-2.14 (m, 1H, CH); 2.14-2.24 (m, 1H, CH₂cod); 2.24-2.33 (m, 2H,CH₂cod, CHcod); 2.33-2.57 (m, 2H, CH₂cod); 3.75 (mbr, 1H, CHcod); 4.16(mbr, 6H, CpH, CHcod); 4.46-4.54 (m, 2H, CH₂O, CHN); 4.68 (m, 1H, CpH);4.72 (m, 1H, CpH); 4.81 (m, 1H, CpH); 4.97 (dd, J=8.8/4.1, 1H, CH₂O);5.00 (mbr, 1H, CHcod); 5.50 (m, 1H, CpH); 7.18-7.22 (m, 2H, ArH);7.41-7.48 (m, 3H, ArH); 7.52 (sbr, 4H, BARF-H); 7.63-7.73 (m, 3H, ArH);7.71 (sbr, 8H, BARF-H); 8.05-8.10 (m, 2H, ArH). ³¹P-NMR (160 MHz,CDCl₃): 93.56 (s, OPAr₂).

Example C12

[0403] Ir catalyst C12 with ligand B12

[0404] Preparation is carried out analogously to Example C1. Columnchromatography (15×2 cm, dichloromethane) yields 262 mg (68%) of anorange-coloured solid.

[0405]¹H-NMR (400 MHz, CDCl₃): δ=1.73 (d, ³J_(HH)=7.0 Hz, 3H, CH₃),1.75-2.05 (brm, 6H, CH₂(COD)), 2.05-2.25 (brm, 1H, CH₂(COD)), 2.27-2.33(brm, 1H, CH₂(COD)), 2.95 (dd, ⁴J_(PH)=5.3 Hz, ³J_(HH)=14.9 Hz, 1H,Ph—CH ₂), 3.04 (d, ²J_(HH)=14.4 Hz, 1H, Ph—CH ₂), 3.15-3.38 (brm, 2H,CH(COD)), 3.42 (d, ²J_(HH)=14.9 Hz, 1H, Ph—CH ₂), 4.10-4.35 (brm, 2H,Ph—CH ₂ and CH(COD)), 4.53 (br, 1H, CH(COD)), 4.75 (d, ²J_(HH)=8.1 Hz,1H, C═N—CH), 5.35 (m, 1H, CH—CH₃), 6.93 (m, 2H, ArH), 7.08 (m, 4H, ArH),7.18 (m, 2H, ArH), 7.23-7.36 (m, 9H, ArH), 7.51 (brs, 4H, ArH(BARF)),7.52-7.69 (m, 7H, ArH), 7.72 (m, 8H, ArH(BARF)), 7.78 (m, 1H, ArH), 8.39(brd, 2H, ArH).

[0406]³¹P{¹H}-NMR (161.9 MHz, CDCl₃): δ=93.6.

Example C13

[0407] Ir Catalyst C13 with Ligand B13

[0408] Preparation is carried out analogously to Example C1. Columnchromatography (15×2 cm, dichloromethane) yields 428 mg (73%) of anorange-coloured solid.

[0409]¹H-NMR (400 MHz, CDCl₃): δ=1.35-1.50 (brm, 2H, CH₂(COD)), 1.47 (d,³J_(HH)=6.32 Hz, 3H, CH₃), 1.55-1.78 (brm, 2H, CH₂(COD)), 2.08-2.52(brm, 5H, CH₂ and CH (COD)), 2.52 (d, ²J_(HH)=15.2 Hz, 1H, Ph—CH ₂),2.89 (m, 2H, Ph—CH ₂), 3.06 (d, ²J_(HH)=15.2 Hz, 1H, Ph—CH ₂), 3.67 (m,1H, CH(COD)), 3.82 (brs, 1H, CH(COD)), 4.57 (s, 1H, C═N—CH), 4.93 (brm,2H, CH—CH₃ and CH(COD)), 6.72 (d, 2H, ²J_(HH)=6.0 Hz, ArH), 7.05-7.18(m, 7H, ArH), 7.35-7.45 (m, 5H, ArH), 7.51 (brs, 4H, ArH(BARF)),7.60-7.71 (m, 13H, ArH), 7.72 (m, 8H, ArH(BARF)), 7.78 (m, 1H, ArH),8.14 (m, 2H, ArH), 8.39 (brd, 2H, ArH).

[0410]³¹P{¹H}-NMR (161.9 MHz, CDCl₃): δ=96.4.

Example C14

[0411] Ir Catalyst C14 with Ligand B14

[0412] Preparation is carried out analogously to Example C1. Columnchromatography (15×2 cm, dichloromethane) yields 229 mg (78%) of anorange-coloured solid.

[0413]¹H-NMR (500 MHz, CDCl₃): δ=1.51-2.10 (brm, 8H, CH₂(COD)), 1.77 (d,³J_(HH)=7.0 Hz, 3H, CH₃), 2.27-2.36 (brm, 2H, CH(COD)), 2.49 (s, 6H,PhCH₃), 2.96 (m, 2H, Ph—CH ₂), 3.42 (m, 2H, Ph—CH ₂), 4.42 (br, 2H,CH(COD)), 4.85 (br, 1H, C═N—CH), 5.34 (m, 1H, CH—CH₃), 6.82 (brs, 2H,ArH), 6.97 (brs, 2H, ArH), 7.15-7.37 (m, 9H, ArH), 7.44 (brs, 4H,ArH(BARF)), 7.50-7.64 (brm, 3H, ArH), 7.72 (m, 8H, ArH(BARF)), 7.73 (br,2H, ArH), 8.02 (brs, 2H, ArH).

[0414]³¹P{¹H}-NMR (161.9 MHz, CDCl₃): δ=93.7.

Example C15

[0415] Ir Catalyst C15 with Ligand B15

[0416] Preparation is carried out analogously to Example C1. Columnchromatography (15×2 cm, dichloromethane) yields 578 mg (68%) of anorange-coloured solid.

[0417]¹H-NMR (500 MHz, CDCl₃): δ=1.25-1.32 (br, 2H, CH₂(COD)), 1.43 (s,18H, C(CH₃)₃), 1.72-2.33 (br, 7H, CH (1H) and CH₂(COD)), 1.87 (d,³J_(HH)=7.0 Hz, 3H, CH₃), 2.95-3.15 and 3.27-3.38 (brm, total 5H, Ph—CH₂ and CH(COD)), 4.17 (br, 1H, CH(COD)), 4.68 (br, 1H, CH(COD)), 4.84(br, 1H, C═N—CH), 5.41 (m, 1H, CH—CH₃), 6.93 (br, 2H, ArH), 7.02 (br,2H, ArH), 7.18 (brm, 2H, ArH), 7.22-7.37 (m, 7H, ArH), 7.51 (brs, 4H,ArH(BARF)), 7.55-7.69 (brm, 6H, ArH), 7.72 (m, 8H, ArH(BARF)), 7.83 (br,2H, ArH), 7.87 (m, 1H, ArH).

[0418]³¹P{¹H}-NMR (161.9 MHz, CDCl₃): δ=92.1.

Example C16

[0419] Ir Catalyst C16 with Ligand B16

[0420] Preparation is carried out analogously to Example C1. Columnchromatography (15×2 cm, diethyl ether/dichloromethane 4/1) yields 152mg (73%) of an orange-coloured solid.

[0421]¹H-NMR (500 MHz, CDCl₃): δ=1.24-1.32 (m, 1H, CH₂(COD)), 1.41 (d,³J_(HH)=7.0 Hz, 3H, CH₃), 1.48-1.57 (brm, 2H, CH₂(COD)), 1.67-1.76 (brm,2H, CH₂(COD)), 2.05-2.15 (brm, 2H, CH₂(COD)), 2.09 (s, 3H, PhCH₃), 2.25(s, 3H, PhCH₃), 2.27-2.34 (brm, 1H, CH₂(COD)), 2.37-2.53 (m, 2H,CH₂(COD) and CH(COD)), 2.75 (m, 2H, Ph—CH ₂), 3.21 (d, ²J_(HH)=14.6 Hz,1H, Ph—CH₂), 3.27 (m, 1H, Ph—CH ₂), 3.47 (m, 1H, CH(COD)), 3.72 (br, 1H,CH(COD)), 4.96 (d, ³J_(HH)=9 Hz, 1H, C═N—CH), 4.98 (br, 1H, CH(COD)),5.32 (m, 1H, CH—CH₃), 6.55-6.65 (m, 3H, ArH), 7.01-7.08 (m, 5H, ArH),7.24-7.18 (m, 2H, ArH) 7.32-7.38 (m, 2H, ArH), 7.39-7.42 (m, 1H, ArH),7.51 (brs, 4H, ArH(BARF)), 7.58-7.68 (brm, 5H, ArH), 7.72 (m, 8H,ArH(BARF)), 7.84 (dt, J=7.5 Hz, J=1.5 Hz, ArH), 8.79 (m, 1H, ArH).

[0422]³¹P{¹H}-NMR (161.9 MHz, CDCl₃): δ=101.1.

Example C17

[0423] Ir Catalyst C17 with Ligand B17

[0424] Preparation is carried out analogously to Example C1. Columnchromatography (15×2 cm, diethyl ether/dichloromethane 4/1) yields 212mg (42%) of an orange-coloured solid.

[0425]¹H-NMR (400 MHz, CDCl₃): δ=0.88 (m, 1H, CH₂cod), 1.27-2.48(complex m, 29H, CH and CH ₂ cyclohexyl, CH₂cod), 2.59 (m, 1H, CHcod),2.82 (d, ²J_(HH)=15.7 Hz, 1H, Ph—CH ₂), 3.04-3.07 (m, 2H, Ph—CH ₂), 3.17(d, ²J_(HH)=14.4 Hz, 1H, Ph—CH ₂), 4.22 (dd, ⁴J_(PH)=2.3 Hz,³J_(HH)=10.4 Hz, 1H, O—CH ₂), 4.42 (t, ³J_(HH)=10.4 Hz, 1H, C═N—CH),4.72 (m, 1H, O—CH ₂), 4.83 (mbr, 1H, CHcod), 5.05 (mbr, 1H, CHcod), 7.04(m, 2H, ArH), 7.23-7.40 (m, 10H, ArH), 7.52 (sbr, 4H, BARH-H), 7.55 (t,J_(HH)=7.6 Hz, 1H, ArH), 7.71 (sbr, 8H, BARF-H), 8.40-8.43 (d,J_(HH)=7.6 Hz, 2H, ArH).

[0426]³¹P{¹H}-NMR (161.9 MHz, CDCl₃): δ=127.0.

Example C18

[0427] Ir Catalyst C18 with Ligand B18

[0428] Preparation is carried out analogously to Example C1. Columnchromatography (15×2 cm, diethyl ether/dichloromethane 4/1) yields 212mg (51%) of an orange-coloured solid.

[0429]¹H-NMR (400 MHz, CDCl₃): δ=0.87 (m, 4H, CH₂cod), 1.26-1.43(complex m, 22H, CH and CH ₂ cyclohexyl, CH₂cod, tert-butyl CH₃),1.44-1.87 (m, 14H, CH and CH ₂ cyclohexyl, CH₂cod), 2.08-2.41 (m, 8H, CHand CH ₂ cyclohexyl, CH₂cod), 2.82 (d, ²J_(HH)=15.2 Hz, 1H, Ph—CH ₂),2.93 (t, ³J_(HH)=7.6 Hz, 1H, Ph—CH ₂), 3.10 (d, ²J_(HH)=15.2 Hz, 1H,Ph—CH ₂), 3.21 (d, ²J_(HH)=14.7 Hz, 1H, Ph—CH ₂), 3.40 (mbr, 2H, CHcod),4.10 (d, J_(HH)=10.6 Hz, 1H, O—CH ₂), 4.40 (t, ³J_(HH)=9.6 Hz, 1H,C═N—CH), 4.48 (mbr, 1H, CHcod), 4.90 (m, 2H, O—CH ₂ and CHcod), 7.02 (m,2H, ArH), 7.19-7.41 (m, 8H, ArH), 7.52 (sbr, 4H, BARH-H), 7.71 (sbr, 8H,BARF-H), 7.85-7.92 (m, 3H, ArH).

[0430]³¹P{¹H}-NMR (161.9 MHz, CDCl₃): δ=126.3.

D) APPLICATION EXAMPLES Example D1

[0431] Hydrogenation of α-trans-methylstilbene

[0432] General Procedure for Hydrogenations

[0433] 105 mg (0.55 mmol) of α-trans-methylstilbene are dissolved with3.5 mg (0.002 mmol) of C1 in 0.5 ml of dichloromethane and transferredto a steel autoclave having a glass insert and magnetic stirrer. Then,at RT, a pressure of 50 bar H₂ is applied. After 13 hours, the pressureis relieved, the solvent is removed and the residue is taken up inheptane and filtered over silica gel. GC/MS analysis (100° C. für 3min., 7° C./min to 250° C.) of the solution shows that conversion iscomplete. The enantiomeric excess is determined by means of chiral HPLC(flow-rate: 0.5 ml/min at 20° C.; stationary phase: Daicel Chiralcel OJ,heptane/isopropanol 99:1) at 97.3% (t_(r): 13.4 (R), 20.4 (S) min.).

[0434] The results are given in Table 1. TABLE 1 Duration ConversionCatalyst mol % [h] [%] ee [%] C1 0.36 5 100 93 (S) C2 0.32 24 100 91.4(R) C9 0.36 14 100 98 (R) C8 0.3 13 100 97 (R) C5 0.36 13 100 97.3 (R)C12 1 2 100 98 (R) C13 1 2 100 97 (R) C14 1 2 100 99 (R) C15 1 2 100 99(R) C16 1 2 100 98 (R) C17 1 2 100 95 (R) C18 1 2 100 97 (S)

Example D2a

[0435] Hydrogenation of (E)-2-(4-methoxyphenyl)-2-butene

[0436] Carried out analogously to D1. Determination of the enantiomericexcess is carried out by means of chiral HPLC [Daicel Chiracel OD-H,heptane/isopropanol 99.99: 0.01) (t_(r): 13.8 (S), 15.5 (R)].

[0437] The results are given in Table 2a. TABLE 2a Duration ConversionCatalyst mol % [h] [%] ee [%] C1 1.2 10 100 83 (S) C4 0.6 6 100 65 (R)C8 0.14 15 100 96 (R) C5 0.2 15 40 45 (R) C11 1.3 8 100 95 (R) C10 1.110 100 93 (R) C9 1.0 8 100 95.5 (R) C12 1 2 >99 99 (R) C13 1 2 >99 98(R) C14 1 2 >99 99 (R) C15 1 2 >99 99 (R) C15 0.1 2 >90 99.4 (R) C16 12 >99 98 (R) C17 1 2 >99 95 (R) C18 1 2 >99 96 (S)

Example D2b

[0438] Hydrogenation of (Z)-2-(4-methoxyphenyl)-2-butene

[0439] Carried out analogously to D1. Determination of the enantiomericexcess is carried out by means of chiral HPLC [Daicel Chiracel OD-H,heptane/isopropanol 99.99: 0.01) (t_(r): 13.8 (S), 15.5 (R)].

[0440] The results are given in Table 2b. TABLE 2b Duration ConversionCatalyst mol % [h] [%] ee [%] C12 1 2 >99 89 (S) C13 1 2 >99 88 (S) C141 2 >99 92 (S) C15 1 2 >99 84 (S) C16 1 2 >99 83 (S)

Example D3

[0441] Hydrogenation of 2-(4-methoxyphenyl)-1-butene

[0442] The hydrogenation is carried out analogously to Example D2.

[0443] The results are given in Table 3. TABLE 3 Duration ConversionCatalyst mol % [h] [%] ee [%] T [° C.] p [bar] C1 0.6 11 100 39 (R) 2550 C4 0.1 14 100 34 (S) 25 50 C9 0.8 1 100  1 (S) 25 50 C8 0.09 120 10067 (S) 25 50 C5 0.18 120 100 47 (S) 25 50 C12 1 0.5 >99 62 (S) 25 50 C121 0.5 >99 89 (S) 0 1 C13 1 0.5 >99 45 (S) 25 50 C14 1 0.5 >99 66 (S) 2550 C14 0.1 0.5 >99 87 (S) 0 1 C15 1 0.5 >99 60 (S) 25 50 C15 1 0.5 >9984 (S) 0 1 C16 1 0.5 >99 52 (S) 25 50 C17 0.1 0.5 >99 84 (S) 25 1 C170.1 0.5 >99 82 (S) 0 1 C18 0.1 0.5 >99 75 (R) 25 1 C18 0.1 0.5 81 85 (R)0 1

Example D4

[0444] Hydrogenation of E-phenylbenzimine

[0445] Carried out analogously to D1. Determination of the enantiomericexcess is carried out by means of chiral HPLC [Daicel Chiracel OD-H,heptane/isopropanol 99:1) (t_(r): 22.6 (S), 29.0 (R)].

[0446] The results are given in Table 4. TABLE 4 Duration ConversionCatalyst mol % [h] [%] ee [%] C1 0.4 16 100 71 (S) C2 0.15 12  82 54 (R)C4 0.92 24 100 48 (R) C7 0.1 16 100 75 (S) C12 1 4 100 68 (R) C13 1 4100 53 (R) C14 1 4 100 39 (R) C15 1 4 100 80 (R) C16 1 4 100 80 (R)

Example D5

[0447] Hydrogenation of trans-β-methylcinnamic acid ethyl ester

[0448] Carried out analogously to D1. Determination of the enantiomericexcess is carried out by means of chiral HPLC [Daicel Chiracel OB-H,heptane/isopropanol 99.5:0.5) (t_(r): 24.3 (S), 29.4 (R)].

[0449] The results are given in Table 4. TABLE 4 Duration ConversionCatalyst mol % [h] [%] ee [%] C12 1 2 >99 92 (R) C13 1 2 97 86 (R) C14 12 >99 94 (R) C15 1 2 94 61 (R) C16 1 2 >99 70 (R) C17 1 2 >99 94 (R) C181 2 >99 86 (S)

What is claimed is:
 1. A compound of formula I or Ia,

wherein X₁ is secondary phosphino; R₃ is hydrogen, a hydrocarbon radicalhaving from 1 to 20 carbon atoms, a heterohydrocarbon radical, bondedvia a carbon atom, having from 2 to 20 atoms and at least one heteroatom selected from the group O, S and NR, or ferrocenyl; R is H orC₁-C₄alkyl; each R₄ individually or both R₄ together are a hydrocarbonradical having from 1 to 20 carbon atoms; and R₀₁ and R₀₂ are eachindependently of the other a hydrogen atom or a hydrocarbon radicalhaving from 1 to 20 carbon atoms.
 2. A compound according to claim 1,wherein the phosphine groups X₁ contain two identical or two differenthydrocarbon radicals having from 1 to 22 carbon atoms or the twohydrocarbon radicals form with the P atom a 3- to 8-membered ring.
 3. Acompound according to claim 2, wherein X₁ is the group -PR₁R₂ wherein R₁and R₂ are each independently of the other a hydrocarbon radical havingfrom 1 to 20 carbon atoms, which is unsubstituted or substituted byhalogen, C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy,(C₆H₅)₃Si, (C₁-C₁₂alkyl)₃Si or by —CO₂—C₁C₆alkyl; or wherein R₁ and R₂together are dimethylene, trimethylene, tetramethylene or pentamethyleneunsubstituted or substituted by C₁-C₄alkyl or by C₁-C₄alkoxy.
 4. Acompound according to claim 3, wherein R₁ and R₂ are identical ordifferent radicals selected from the group: branched C₃-C₆alkyl;cyclopentyl or cyclohexyl unsubstituted or substituted by from one tothree C₁-C₄alkyl or C₁-C₄alkoxy substituents; benzyl unsubstituted orsubstituted by from one to three C₁-C₄alkyl or C₁-C₄alkoxy substituents,and phenyl unsubstituted or substituted by from one to three C₁-C₄alkyl,C₁-C₄alkoxy, —NH₂, OH, F, Cl, C₁-C₄fluoroalkyl or C₁-C₄fluoroalkoxysubstituents.
 5. A compound according to claim 3, wherein R₁ and R₂ areidentical or different radicals selected from the group: phenylunsubstituted or substituted by from one to three C₁-C₄alkyl,C₁-C₄alkoxy or C₁-C₄fluoroalkyl substituents.
 6. A compound according toclaim 1, wherein the hydrocarbon radical R₃ contains from 1 to 16 carbonatoms and the heterohydrocarbon radical R₃ contains from 1 to 16 atomsand from 1 to 3 hetero atoms selected from the group O, S and NR.
 7. Acompound according to claim 6, wherein the hydrocarbon radical R₃ isC₁-C₁₈alkyl; C₃-C₁₂cycloalkyl; or C₆-C₁₆aryl, and the heterohydrocarbonradical R₃ is C₁-C₁₈heteroalkyl, C₃-C₁₂heterocycloalkyl orC₄-C₁₆heteroaryl.
 8. A compound according to claim 7, wherein R₃ is ahydrocarbon radical selected from the group: branched C₃-C₁₂alkyl,C₅-C₆cycloalkyl and C₆-C₁₂aryl, the cyclic radicals being unsubstitutedor substituted by halogen, C₁-C₄alkyl or by C₁-C₄alkoxy.
 9. A compoundaccording to claim 1, wherein R₄ is a hydrocarbon radical selected fromthe group: branched C₃-C₁₂alkyl, C₅-C₆cycloalkyl, C₆-C₁₂aryl andC₇-C₁₂aralkyl, the cyclic radicals being unsubstituted or substituted byhalogen, C₁-C₄alkyl, Cl-C₄haloalkyl or by C₁-C₄alkoxy.
 10. A compoundaccording to claim 1, wherein R₀₁ and R₀₂ are each independently of theother H, C₁-C₁₂alkyl, C₅-C₆cycloalkyl, C₆-C₁₂aryl or C₇-C₁₂aralkyl, thecyclic radicals being unsubstituted or substituted by halogen,C₁-C₄alkyl, C₁-C₄haloalkyl or by C₁-C₄alkoxy.
 11. A compound accordingto claim 1, which corresponds to formula Ib or Ic

wherein X₁ is —PR₁R₂, R₀₁ is hydrogen or C₁-C₄alkyl, R₁ and R₂ areidentical or different and are selected from the group: α-branchedC₃-C₆alkyl; C₅-C₇cycloalkyl unsubstituted or substituted by from one tothree C₁-C₄alkyl or C₁-C₄alkoxy substituents; phenyl unsubstituted orsubstituted by from one to three C₁-C₄alkyl, C₁-C₄-alkoxy orC₁-C₄fluoroalkyl substituents; and dimethylene, trimethylene,tetramethylene or hexamethylene unsubstituted or substituted byC₁-C₄alkyl or by C₁-C₄alkoxy; R₃ is a hydrocarbon radical selected fromthe group: branched C₃-C₁₂alkyl, C₅-C₆cycloalkyl, C₆-C₁₂aryl andferrocenyl, the cyclic radicals being unsubstituted or substituted byhalogen, C₁-C₄alkyl, C₁-C₄haloalkyl or by C₁-C₄alkoxy; and R₄ is ahydrocarbon radical selected from the group: branched C₃-C₁₂alkyl,C₅-C₆cycloalkyl, C₆-C₁₂aryl and C₇-C₁₂aralkyl, the cyclic radicals beingunsubstituted or substituted by halogen, C₁-C₄alkyl or by C₁-C₄alkoxy.12. A process for the preparation of a compound of formula I or Ia,

wherein R₀₁, R₀₂, R₃, R₄ and X₁ are as defined above, and ˜ denotes theR- or S-form, in which process either a1) a compound of formula II

or a salt thereof, wherein R₃ is as defined above and R₈ is C₁-C₄alkyl,is reacted with at least an equivalent amount of a compound of formulaIII,

wherein R₉ is C₁-C₄alkyl, to form a compound of formula IV,

a2) the compound of formula IV is reacted with at least 2 equivalents ofan organometal compound of formula V or Va R₄—X₂ (V), R₄—(X₂)₂ (Va),wherein R₄ is as defined above, X₂ is an alkali metal or —Me₁X₃, Me₁ isMg or Zn, and X₃ is Cl, Br or I, to form a compound of formula VI

and a3) the hydroxyl group in the compound of formula VI is metallatedand then reacted with a halophosphine of formula VII, X₁—Y₁  (VII),wherein X₁ is as defined above and Y₁ is Cl, Br or I, to form a compoundof formula Ia or Ib; or b1) a carboxylic acid of formula VIIIR₃—COOH  (VIII), or a derivative of that carboxylic acid, is reactedwith a compound of formula III to form a carboxylic acid amide offormula IX,

b2) the compound of formula IX is reacted with a compound of formula Vor Va to form a compound of formula X,

b3) the compound of formula X is cyclised to form a compound of formulaVI; and b4) the hydroxyl group in the compound of formula VI ismetallated and then reacted with a halophosphine of formula VII to forma compound of formula Ia or Ib.
 13. A compound of formula IV

wherein R₃ is as defined in claim 1, R₀₁ is a hydrogen atom and R₀₂ is ahydrocarbon radical having from 1 to 20 carbon atoms, and R₉ isC₁-C₄alkyl.
 14. A compound of formula VI

wherein R₃ and R₄ are as defined in claim 1, and R₀₁ and R₀₂ are eachindependently of the other a hydrogen atom or a hydrocarbon radicalhaving from 1 to 20 carbon atoms.
 15. A compound of formula X

wherein R₀₁, R₀₂, R₃ and R₄ are as defined in claim
 1. 16. A metalcomplex of a metal selected from the group of TM8 metals with a compoundof formula I or Ia as ligand.
 17. A metal complex according to claim 16,wherein the TM metal is Cu, Ag, Au, Ni, Co, Rh, Ru, Pd, Ir or Pt.
 18. Ametal complex according to claim 17, wherein the TM metal is rhodium,iridium, ruthenium, platinum or palladium.
 19. A metal complex accordingto claim 16, wherein the metal complex corresponds to formula XI or XIIA₁MeL_(n) (XI), (A₁MeL_(n))^((z+))(E⁻)_(z) (XII), wherein A₁ is acompound of formula I or Ia, L denotes identical or different,monodentate, anionic or non-ionic ligands, or two L denote identical ordifferent, bidentate, anionic or non-ionic ligands; n is 2, 3 or 4 whenL is a monodentate ligand, or n is 1 or 2 when L is a bidentate ligand;z is 1, 2 or 3; Me is a metal selected from the group Rh, Ir and Ru; themetal having the oxidation state 0, 1, 2, 3 or 4; E⁻ is the anion of anoxyacid or complex acid; and the anionic ligands balance the charge ofoxidation states 1, 2, 3 or 4 of the metal.
 20. A metal complexaccording to claim 19, wherein E is —Cl³¹, —Br⁻, —I³¹ , ClO₄ ⁻, CF₃SO₃⁻, CH₃SO₃ ⁻, HSO₄ ⁻, (CF₃SO₂)₂N⁻, (CF₃SO₂)₃C³¹ , B(phenyl)₄ ⁻,B[bis(3,5-trifluoromethyl)phenyl]₄ ⁻, B[bis(3,5-dimethyl)phenyl]₄ ⁻,B(C₆F₅)₄ ⁻, B(4-methylphenyl)₄ ⁻, BF₄ ⁻, PF₆ ⁻, SbCl₆ ⁻, AsF₆ ⁻ or SbF₆⁻.
 21. A metal complex according to claim 16, which corresponds toformula XIII or XIV [A₁Me₂YZ] (XIII), [A₁Me₂Y]⁺E₁ ⁻ (XIV), wherein A₁ isa compound of formula I or Ia; Me₂ is rhodium or iridium; Y denotes twoolefins or a diene; Z is Cl, Br or I; and E₁ ⁻ is the anion of anoxyacid or complex acid.
 22. A metal complex according to claim 20,wherein Y is a C₂-C₁₂olefin, the diene contains from 5 to 12 carbonatoms, and Z is Cl or Br, and E₁ is BF₄ ⁻, ClO₄ ⁻, CF₃SO₃ ⁻, CH₃SO₃ ⁻,HSO₄ ⁻, B(phenyl)₄ ⁻, B[bis(3,5-trifluoromethyl)phenyl]₄ ⁻, PF₆ ⁻, SbCl₆⁻, AsF₆ ⁻ or SbF₆ ⁻.
 23. A process for the preparation of chiral organiccompounds by asymmetric addition of hydrogen, borohydrides or silanes toa carbon-carbon or carbon-hetero atom multiple bond in prochiral organiccompounds or asymmetric addition of C-nucleophiles or amines to allylcompounds in the presence of a catalyst, wherein the addition is carriedout in the presence of catalytic amounts of at least one metal complexaccording to claim
 16. 24. Use of a metal complex according to claim 16as a homogeneous catalyst in the preparation of chiral organic compoundsby asymmetric addition of hydrogen, borohydrides or silanes to acarbon-carbon or carbon-hetero atom multiple bond in prochiral organiccompounds or asymmetric addition of C-nucleophiles or amines to allylcompounds.